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Identification
NameMethotrexate
Accession NumberDB00563  (APRD00353)
TypeSmall Molecule
GroupsApproved
DescriptionAn antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [PubChem]
Structure
Thumb
Synonyms
4-amino-10-methylfolic acid
4-amino-N(10)-Methylpteroylglutamic acid
Amethopterin
Emtexate
Ledertrexate
Methotrexat
Méthotrexate
Methotrexatum
Metotrexato
MTX
N-[4-[[(2,4-Diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid
Rheumatrex
Trexall
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Jamp-methotrexateSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousJamp Pharma Corporation2014-03-12Not applicableCanada
MethotrexateTablet2.5 mgOralPfizer Canada Inc1996-11-15Not applicableCanada
MethotrexateTablet2.5 mg/1OralDispensing Solutions, Inc.1953-12-07Not applicableUs
MethotrexateSolution25 mgIntra-arterial; Intramuscular; IntravenousPfizer Canada Inc1997-01-242011-05-03Canada
MethotrexateTablet2.5 mg/1OralMajor Pharmaceuticals2009-06-01Not applicableUs
MethotrexateTablet2.5 mg/1OralREMEDYREPACK INC.2015-09-23Not applicableUs
MethotrexateTablet2.5 mg/1OralDAVA Pharmaceuticals, Inc.1953-12-07Not applicableUs
MethotrexateTablet2.5 mg/1OralRebel Distributors Corp1953-12-07Not applicableUs
MethotrexateTablet2.5 mg/1OralA S Medication Solutions1953-12-07Not applicableUs
MethotrexateTablet2.5 mg/1OralA S Medication Solutions1953-12-07Not applicableUs
MethotrexateTablet2.5 mg/1OralPd Rx Pharmaceuticals, Inc.1953-12-07Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; IntravenousHospira Worldwide, Inc.1959-08-10Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousHospira Worldwide, Inc.1959-08-10Not applicableUs
Methotrexate Dbl Inj 10mg/mlLiquid10 mgIntravenousDavid Bull Laboratories (Pty) Ltd.1985-12-311997-08-14Canada
Methotrexate Dbl Inj 2.5mg/mlLiquid2.5 mgIntravenousDavid Bull Laboratories (Pty) Ltd.1985-12-311998-08-13Canada
Methotrexate Dbl Inj 25mg/mlLiquid25 mgIntravenousDavid Bull Laboratories (Pty) Ltd.1985-12-311998-08-13Canada
Methotrexate Injection BPSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousUman Pharma IncNot applicableNot applicableCanada
Methotrexate Injection USPSolution25 mgIntra-arterial; Intramuscular; IntravenousSandoz Canada Incorporated2013-02-14Not applicableCanada
Methotrexate Injection, BPSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousPharmascience Inc2014-05-08Not applicableCanada
Methotrexate Injection, BPSolution7.5 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousPharmascience Inc2014-05-08Not applicableCanada
Methotrexate Injection, BPSolution10 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousPharmascience Inc2014-05-08Not applicableCanada
Methotrexate Injection, BPSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousAccord Healthcare Inc2011-09-30Not applicableCanada
Methotrexate Injection, BPSolution15 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousPharmascience Inc2014-05-08Not applicableCanada
Methotrexate Injection, BPSolution20 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousPharmascience Inc2014-05-08Not applicableCanada
Methotrexate Injection, USPSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Pharmaceuticals Ulc2014-08-14Not applicableCanada
Methotrexate Injection, USPSolution10 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousHospira Healthcare Corporation1997-07-30Not applicableCanada
Methotrexate Injection, USPSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousHospira Healthcare Corporation1998-07-13Not applicableCanada
Methotrexate Injection, USPSolution25 mgIntra-arterial; Intramuscular; IntravenousHospira Healthcare Corporation1998-04-30Not applicableCanada
Methotrexate Injection, USPSolution25 mgIntravenousHospira Healthcare Corporation1997-07-30Not applicableCanada
Methotrexate PF/sa InjectionSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Methotrexate Sod Inj 25mg/ml USPLiquid25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousDavid Bull Laboratories (Pty) Ltd.1990-12-311998-08-13Canada
Methotrexate SodiumTablet2.5 mg/1OralGen Pak Solutions Llc2012-10-01Not applicableUs
Methotrexate Sodium Inj 20mgPowder, for solution20 mgIntramuscular; Intrathecal; IntravenousLederle Cyanamid Canada Inc.1977-12-311997-08-14Canada
Methotrexate Sodium Inj 25.0mg/mlLiquid25 mgIntramuscular; Intrathecal; IntravenousLederle Cyanamid Canada Inc.1976-12-311997-08-14Canada
Methotrexate Sodium Inj 25mg/mlLiquid50 mgIntramuscular; Intrathecal; IntravenousLederle Cyanamid Canada Inc.1981-12-311997-08-14Canada
Methotrexate Sodium Inj 25mg/ml USPLiquid25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousDavid Bull Laboratories (Pty) Ltd.1992-12-311999-08-10Canada
Methotrexate Sodium InjectionSolution25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousTeva Canada Limited1995-12-31Not applicableCanada
Methotrexate Sodium Injection USPSolution25 mgIntra-arterial; Intramuscular; Intrathecal; Intravenous; IntraventricularPfizer Canada Inc1996-09-052006-08-02Canada
Methotrexate Tab 2.5mgTablet2.5 mgOralLederle Cyanamid Canada Inc.1955-12-311997-08-14Canada
Methotrexate Tab 2.5mg USPTablet2.5 mgOralDavid Bull Laboratories (Pty) Ltd.1991-12-312000-08-01Canada
Methotrexate Tablets, USPTablet10 mgOralHospira Healthcare Corporation2004-04-12Not applicableCanada
Methotrexate-liq Im IV Iar Int Ivr 25mg/mlLiquid25 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousWyeth Ayerst Canada Inc.1997-02-042001-09-19Canada
Methotrexate-pws Im IV Iar Int Ivr 20mg/vialPowder, for solution20 mgIntra-arterial; Intramuscular; Intrathecal; IntravenousWyeth Ayerst Canada Inc.1997-02-042001-05-22Canada
MetojectSolution15 mgIntra-arterial; Intramuscular; IntravenousMedexus Inc2009-01-26Not applicableCanada
MetojectSolution25 mgIntra-arterial; Intramuscular; IntravenousMedexus Inc2009-01-26Not applicableCanada
MetojectSolution20 mgIntra-arterial; Intramuscular; IntravenousMedexus Inc2008-05-30Not applicableCanada
MetojectSolution7.5 mgIntra-arterial; Intramuscular; IntravenousMedexus Inc2009-01-26Not applicableCanada
MetojectSolution10 mgIntra-arterial; Intramuscular; IntravenousMedexus Inc2009-01-26Not applicableCanada
Metoject SubcutaneousSolution10 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
Metoject SubcutaneousSolution17.5 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
Metoject SubcutaneousSolution15 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
Metoject SubcutaneousSolution22.5 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
Metoject SubcutaneousSolution20 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
Metoject SubcutaneousSolution7.5 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
Metoject SubcutaneousSolution25 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
Metoject SubcutaneousSolution12.5 mgSubcutaneousMedexus IncNot applicableNot applicableCanada
NordimetInjection, solution22.5 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
NordimetInjection, solution15 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
NordimetInjection, solution7.5 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
NordimetInjection, solution17.5 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
NordimetInjection, solution10 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
NordimetInjection, solution20 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
NordimetInjection, solution25 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
NordimetInjection, solution12.5 mgSubcutaneousNordic Group B.V.2016-08-18Not applicableEu
OtrexupInjection, solution12.5 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
OtrexupInjection, solution15 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
OtrexupInjection, solution17.5 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
OtrexupInjection, solution20 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
OtrexupInjection, solution22.5 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
OtrexupInjection, solution25 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
OtrexupInjection, solution10 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
OtrexupInjection, solution7.5 mg/.4mLSubcutaneousAntares Pharma, Inc.2013-10-11Not applicableUs
RasuvoInjection, solution17.5 mg/.35mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution27.5 mg/.55mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution10 mg/.2mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution20 mg/.4mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution30 mg/.6mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution12.5 mg/.25mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution22.5 mg/.45mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution15 mg/.3mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution25 mg/.5mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
RasuvoInjection, solution7.5 mg/.15mLSubcutaneousMedac Pharma, Inc2014-07-10Not applicableUs
Ratio-methotrexate SodiumTablet2.5 mgOralTeva Canada Limited2001-11-14Not applicableCanada
Rheumatrex Dose PackTablet2.5 mg/1OralDAVA Pharmaceuticals, Inc.1953-07-12Not applicableUs
Rheumatrex Tab 2.5mgTablet2.5 mgOralLederle Cyanamid Canada Inc.1990-12-312000-08-02Canada
Rheumatrex-tab 2.5mgTablet2.5 mgOralWyeth Ayerst Canada Inc.1999-04-122000-08-02Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-methotrexateTablet2.5 mgOralHospira Healthcare Corporation1999-09-17Not applicableCanada
Apo-methotrexateTablet2.5 mgOralApotex IncNot applicableNot applicableCanada
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Institutional LLC2012-03-30Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousTeva Parenteral Medicines, Inc.2012-08-012016-01-22Us
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPfizer Laboratories Div Pfizer Inc.2012-03-30Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Institutional LLC2012-03-30Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousFresenius Kabi USA, LLC2003-04-03Not applicableUs
MethotrexateTablet2.5 mg/1OralPd Rx Pharmaceuticals, Inc.1990-11-01Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousTeva Parenteral Medicines, Inc.2012-08-01Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPfizer Laboratories Div Pfizer Inc.2012-03-30Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Institutional LLC2012-03-30Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousAccord Healthcare, Inc.2014-02-01Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; IntravenousFresenius Kabi USA, LLC2001-09-10Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPfizer Laboratories Div Pfizer Inc.2012-03-30Not applicableUs
MethotrexateInjection, powder, lyophilized, for solution1 g/1Intra-arterial; Intramuscular; Intrathecal; IntravenousFresenius Kabi USA, LLC2000-01-22Not applicableUs
MethotrexateInjection, solution1 g/40mLIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Institutional LLC2012-06-27Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Institutional LLC2012-03-30Not applicableUs
MethotrexateTablet2.5 mg/1OralA S Medication Solutions1990-11-01Not applicableUs
MethotrexateTablet2.5 mg/1OralRebel Distributors Corp1990-10-15Not applicableUs
MethotrexateTablet2.5 mg/1OralMylan Pharmaceuticals Inc.1992-05-18Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPfizer Laboratories Div Pfizer Inc.2012-03-30Not applicableUs
MethotrexateTablet2.5 mg/1OralBarr Laboratories Inc.1990-11-01Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Institutional LLC2012-03-30Not applicableUs
MethotrexateTablet2.5 mg/1OralMylan Institutional Inc.1995-07-13Not applicableUs
MethotrexateTablet2.5 mg/1OralAv Kare, Inc.2014-11-20Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousTeva Parenteral Medicines, Inc.2012-07-31Not applicableUs
MethotrexateInjection25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPfizer Laboratories Div Pfizer Inc.2012-03-30Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPhysicians Total Care, Inc.2003-03-26Not applicableUs
MethotrexateInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousTeva Parenteral Medicines, Inc.2012-08-01Not applicableUs
Methotrexate SodiumTablet2.5 mg/1OralPhysicians Total Care, Inc.2007-12-05Not applicableUs
Methotrexate SodiumTablet2.5 mg/1OralWest Ward Pharmaceuticals Corp.1994-08-01Not applicableUs
Methotrexate SodiumInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousSandoz Inc2009-06-01Not applicableUs
Methotrexate SodiumTablet2.5 mg/1OralWest Ward Pharmaceuticals Corp.1994-08-01Not applicableUs
Methotrexate SodiumTablet2.5 mg/1OralREMEDYREPACK INC.2011-06-20Not applicableUs
Methotrexate SodiumInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPfizer Laboratories Div Pfizer Inc.2012-03-30Not applicableUs
Methotrexate SodiumTablet2.5 mg/1Oralbryant ranch prepack1994-08-01Not applicableUs
Methotrexate SodiumTablet2.5 mg/1OralREMEDYREPACK INC.2011-07-21Not applicableUs
Methotrexate SodiumInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousMylan Institutional LLC2012-03-30Not applicableUs
Methotrexate SodiumInjection, solution25 mg/mLIntra-arterial; Intramuscular; Intrathecal; IntravenousSandoz Inc2009-06-01Not applicableUs
TrexallTablet, film coated10 mg/1OralTeva Women's Health, Inc.2001-05-03Not applicableUs
TrexallTablet, film coated15 mg/1OralTeva Women's Health, Inc.2001-05-03Not applicableUs
TrexallTablet, film coated5 mg/1OralTeva Women's Health, Inc.2001-05-03Not applicableUs
TrexallTablet, film coated7.5 mg/1OralTeva Women's Health, Inc.2001-05-03Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AbitrexateTeva
AlltrexNaprod
ArtraitTRB
AtrexelSchering-Plough
BendatrexatBendalis
CarditrexCadila
DermotrexEast West
EbetrexEbewe
EmtexateNot Available
LedertrexateBiodim
MaxtrexPfizer
MeisushengHospira
MexateCadila HC
RheumatrexWyeth KK
TrexanAtafarm
ZexateDabur Pharma
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Methotrexate Sodium
7413-34-5
Thumb
  • InChI Key: DASQOOZCTWOQPA-GXKRWWSZSA-L
  • Monoisotopic Mass: 498.13520514
  • Average Mass: 498.4029
DBSALT000115
Categories
UNIIYL5FZ2Y5U1
CAS number59-05-2
WeightAverage: 454.4393
Monoisotopic: 454.171315854
Chemical FormulaC20H22N8O5
InChI KeyFBOZXECLQNJBKD-ZDUSSCGKSA-N
InChI
InChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
IUPAC Name
(2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid
SMILES
CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O
Pharmacology
IndicationMethotrexate is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. In acute lymphocytic leukemia, methotrexate is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. Methotrexate is also indicated in the treatment of meningeal leukemia. Methotrexate is used alone or in combination with other anticancer agents in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T cell lymphoma), and lung cancer, particularly squamous cell and small cell types. Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas. Methotrexate is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis. Methotrexate is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis.
Structured Indications
PharmacodynamicsMethotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). Methotrexate is also indicated in the management of severe, active, classical, or definite rheumatoid arthritis.
Mechanism of actionMethotrexate anti-tumor activity is a result of the inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known.
TargetKindPharmacological actionActionsOrganismUniProt ID
Dihydrofolate reductaseProteinyes
inhibitor
HumanP00374 details
Related Articles
AbsorptionOral absorption is dose dependent in adults and leukemic pediatric patients. In adults, peak serum levels are reached within one to two hours. At doses of 30 mg/m^2 or less, methotrexate is generally well absorbed with a mean bioavailability of 60%. At doses greater than 80 mg/m^2, the absorption of the doses is significantly less due to a saturation effect.
Volume of distribution
  • 0.18 L/kg [initial volume of distribution (Vd)]
  • 0.4 – 0.8 L/kg [steady state Vd]
    Methotrexate competes with reduced folates for active transport across cell membranes by means of a single carrier-mediated active transport process. At serum concentrations greater than 100 micromolar, passive diffusion becomes a major pathway by which effective intracellular concentrations can be achieved. Methotrexate does not cross the blood-brain-barrier.
Protein binding50% bound to protein, primarily to albumin
Metabolism

Methotrexate undergoes hepatic and intracellular metabolism to polyglutamated forms which can be converted back to methotrexate by hydroxylase enzymes. These polyglutamates act as inhibitors of dihydrofolate reductase and thymidylate synthetase. A small amount of metabolism to 7-hydroxymethotrexate may occur at doses commonly prescribed. Furthermore, intestinal flora partially metabolizes methotrexate after oral administration.

SubstrateEnzymesProduct
Methotrexate
7-hydroxymethotrexateDetails
Route of eliminationRenal excretion is the primary route of elimination and is dependent upon dosage and route of administration. IV administration, 80% to 90% of the administered dose is excreted unchanged in the urine within 24 hours. There is limited biliary excretion amounting to 10% or less of the administered dose.
Half lifeLow doses (less than 30 mg/m^2): 3 to 10 hours; High doses: 8 to 15 hours.
Clearance

Methotrexate clearance rates vary widely and are generally decreased at higher doses. Delayed drug clearance has been identified as one of the major factors responsible for methotrexate toxicity.

ToxicitySymptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD50=43mg/kg(orally in rat).
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Methotrexate Action PathwayDrug actionSMP00432
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Canalicular multispecific organic anion transporter 1
Gene symbol: ABCC2
UniProt: Q92887
Not AvailableABCC2 IVS 23+56T alleleGeneral toxicity (gastrointestinal and hepatotoxicity)18381794
Methylenetetrahydrofolate reductase
Gene symbol: MTHFR
UniProt: P42898
rs1801133 Not AvailableT alleleMucositis, hepatic toxicity, thrombocytopenia, alopecia17488658
Interactions
Drug Interactions
DrugInteractionDrug group
AceclofenacThe serum concentration of Methotrexate can be increased when it is combined with Aceclofenac.Approved
AcetaminophenThe serum concentration of Methotrexate can be increased when it is combined with Acetaminophen.Approved
AcetovanilloneThe serum concentration of Methotrexate can be increased when it is combined with Acetovanillone.Investigational
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Methotrexate.Approved
Acetylsalicylic acidThe serum concentration of Methotrexate can be increased when it is combined with Acetylsalicylic acid.Approved, Vet Approved
AcitretinAcitretin may increase the hepatotoxic activities of Methotrexate.Approved
AdapaleneThe serum concentration of Methotrexate can be increased when it is combined with Adapalene.Approved
AfatinibThe serum concentration of Methotrexate can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Methotrexate can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Methotrexate can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Methotrexate can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Methotrexate can be increased when it is combined with Alfentanil.Approved, Illicit
AlitretinoinAlitretinoin may increase the hepatotoxic activities of Methotrexate.Approved, Investigational
ALT-110The risk or severity of adverse effects can be increased when Methotrexate is combined with ALT-110.Investigational
AmantadineThe serum concentration of Methotrexate can be increased when it is combined with Amantadine.Approved
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be increased when it is combined with Methotrexate.Experimental
AmdinocillinThe serum concentration of Methotrexate can be increased when it is combined with Amdinocillin.Withdrawn
Aminohippuric acidThe serum concentration of Methotrexate can be increased when it is combined with Aminohippuric acid.Approved
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Methotrexate.Approved
Aminosalicylic AcidThe serum concentration of Methotrexate can be increased when it is combined with Aminosalicylic Acid.Approved
AmiodaroneThe serum concentration of Methotrexate can be decreased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Methotrexate can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Methotrexate can be increased when it is combined with Amlodipine.Approved
AmoxicillinThe serum concentration of Methotrexate can be increased when it is combined with Amoxicillin.Approved, Vet Approved
AmpicillinThe serum concentration of Methotrexate can be increased when it is combined with Ampicillin.Approved, Vet Approved
AmprenavirThe serum concentration of Methotrexate can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Methotrexate can be increased when it is combined with Amsacrine.Approved
AnisodamineThe serum concentration of Methotrexate can be increased when it is combined with Anisodamine.Investigational
AntipyrineThe serum concentration of Methotrexate can be increased when it is combined with Antipyrine.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Methotrexate.Investigational
ApremilastThe serum concentration of Methotrexate can be increased when it is combined with Apremilast.Approved, Investigational
AstemizoleThe serum concentration of Methotrexate can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Methotrexate can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Methotrexate can be increased when it is combined with Atenolol.Approved
AtorvastatinThe serum concentration of Methotrexate can be increased when it is combined with Atorvastatin.Approved
AzapropazoneThe serum concentration of Methotrexate can be increased when it is combined with Azapropazone.Withdrawn
AzelastineThe serum concentration of Methotrexate can be increased when it is combined with Azelastine.Approved
AzidocillinThe serum concentration of Methotrexate can be increased when it is combined with Azidocillin.Approved
AzithromycinThe serum concentration of Methotrexate can be increased when it is combined with Azithromycin.Approved
AzlocillinThe serum concentration of Methotrexate can be increased when it is combined with Azlocillin.Approved
BacampicillinThe serum concentration of Methotrexate can be increased when it is combined with Bacampicillin.Approved
BalsalazideThe serum concentration of Methotrexate can be increased when it is combined with Balsalazide.Approved, Investigational
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Methotrexate.Investigational
BenoxaprofenThe serum concentration of Methotrexate can be increased when it is combined with Benoxaprofen.Withdrawn
Benzathine benzylpenicillinThe serum concentration of Methotrexate can be increased when it is combined with Benzathine benzylpenicillin.Approved, Vet Approved
BenzocaineThe serum concentration of Methotrexate can be increased when it is combined with Benzocaine.Approved
BenzylpenicillinThe serum concentration of Methotrexate can be increased when it is combined with Benzylpenicillin.Approved, Vet Approved
Benzylpenicillin PotassiumThe serum concentration of Methotrexate can be increased when it is combined with Benzylpenicillin Potassium.Approved
Benzylpenicilloyl PolylysineThe serum concentration of Methotrexate can be increased when it is combined with Benzylpenicilloyl Polylysine.Approved
BepridilThe serum concentration of Methotrexate can be increased when it is combined with Bepridil.Approved, Withdrawn
Betulinic AcidThe serum concentration of Methotrexate can be increased when it is combined with Betulinic Acid.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Methotrexate.Approved, Investigational
BiperidenThe serum concentration of Methotrexate can be increased when it is combined with Biperiden.Approved
BosutinibThe serum concentration of Methotrexate can be increased when it is combined with Bosutinib.Approved
BromfenacThe serum concentration of Methotrexate can be increased when it is combined with Bromfenac.Approved
BromocriptineThe serum concentration of Methotrexate can be increased when it is combined with Bromocriptine.Approved, Investigational
BucillamineThe serum concentration of Methotrexate can be increased when it is combined with Bucillamine.Investigational
BumetanideThe therapeutic efficacy of Bumetanide can be decreased when used in combination with Methotrexate.Approved
BuprenorphineThe serum concentration of Methotrexate can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Methotrexate can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Methotrexate.Approved
CaffeineThe serum concentration of Methotrexate can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Methotrexate can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Methotrexate can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Methotrexate can be increased when it is combined with Captopril.Approved
CarbamazepineThe serum concentration of Methotrexate can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarbenicillinThe serum concentration of Methotrexate can be increased when it is combined with Carbenicillin.Approved
CarindacillinThe serum concentration of Methotrexate can be increased when it is combined with Carindacillin.Approved
CarprofenThe serum concentration of Methotrexate can be increased when it is combined with Carprofen.Approved, Vet Approved, Withdrawn
CarvedilolThe serum concentration of Methotrexate can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Methotrexate can be increased when it is combined with Caspofungin.Approved
CastanospermineThe serum concentration of Methotrexate can be increased when it is combined with Castanospermine.Experimental
CDX-110The risk or severity of adverse effects can be increased when Methotrexate is combined with CDX-110.Investigational
CelecoxibThe serum concentration of Methotrexate can be increased when it is combined with Celecoxib.Approved, Investigational
ChloroquineThe serum concentration of Methotrexate can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Methotrexate can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Methotrexate can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Methotrexate can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Methotrexate can be increased when it is combined with Cholesterol.Experimental
CholestyramineCholestyramine can cause a decrease in the absorption of Methotrexate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Cholic AcidThe serum concentration of Methotrexate can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Methotrexate can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Methotrexate can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Methotrexate can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Methotrexate can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Methotrexate can be increased when it is combined with Clarithromycin.Approved
ClofazimineThe serum concentration of Methotrexate can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Methotrexate can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClonixinThe serum concentration of Methotrexate can be increased when it is combined with Clonixin.Approved
ClotrimazoleThe serum concentration of Methotrexate can be decreased when it is combined with Clotrimazole.Approved, Vet Approved
CloxacillinThe serum concentration of Methotrexate can be increased when it is combined with Cloxacillin.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Methotrexate is combined with Clozapine.Approved
CobicistatThe serum concentration of Methotrexate can be increased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Methotrexate can be increased when it is combined with Colchicine.Approved
ColesevelamColesevelam can cause a decrease in the absorption of Methotrexate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ColestipolColestipol can cause a decrease in the absorption of Methotrexate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ColforsinThe serum concentration of Methotrexate can be increased when it is combined with Colforsin.Experimental
CrizotinibThe serum concentration of Methotrexate can be increased when it is combined with Crizotinib.Approved
CurcuminThe serum concentration of Methotrexate can be increased when it is combined with Curcumin.Investigational
CyclacillinThe serum concentration of Methotrexate can be increased when it is combined with Cyclacillin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Methotrexate.Approved, Investigational
CyclosporineThe serum concentration of Methotrexate can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclosporineThe serum concentration of Methotrexate can be decreased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
D-LimoneneThe serum concentration of Methotrexate can be increased when it is combined with D-Limonene.Investigational
DaclatasvirThe serum concentration of Methotrexate can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Methotrexate can be increased when it is combined with Dactinomycin.Approved
DasatinibThe serum concentration of Methotrexate can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Methotrexate can be decreased when it is combined with Daunorubicin.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Methotrexate.Approved
dersalazineThe serum concentration of Methotrexate can be increased when it is combined with dersalazine.Investigational
DesipramineThe serum concentration of Methotrexate can be increased when it is combined with Desipramine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Methotrexate.Approved
DesloratadineThe serum concentration of Methotrexate can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Methotrexate can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DexketoprofenThe serum concentration of Methotrexate can be increased when it is combined with Dexketoprofen.Approved
DextromethorphanThe serum concentration of Methotrexate can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Methotrexate can be increased when it is combined with Diclofenac.Approved, Vet Approved
DicloxacillinThe serum concentration of Methotrexate can be increased when it is combined with Dicloxacillin.Approved, Vet Approved
DiflunisalThe serum concentration of Methotrexate can be increased when it is combined with Diflunisal.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Methotrexate.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Methotrexate.Approved
DihydroergotamineThe serum concentration of Methotrexate can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Methotrexate can be increased when it is combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Methotrexate can be increased when it is combined with Dipyridamole.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Methotrexate.Approved, Investigational
DoxazosinThe serum concentration of Methotrexate can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Methotrexate can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Methotrexate can be decreased when it is combined with Doxorubicin.Approved, Investigational
DronabinolThe serum concentration of Methotrexate can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Methotrexate can be increased when it is combined with Dronedarone.Approved
DroxicamThe serum concentration of Methotrexate can be increased when it is combined with Droxicam.Approved
DuvelisibThe serum concentration of Methotrexate can be increased when it is combined with Duvelisib.Investigational
DyphyllineThe serum concentration of Dyphylline can be increased when it is combined with Methotrexate.Approved
E6201The serum concentration of Methotrexate can be increased when it is combined with E6201.Investigational
EbselenThe serum concentration of Methotrexate can be increased when it is combined with Ebselen.Investigational
ElbasvirThe serum concentration of Methotrexate can be increased when it is combined with Elbasvir.Approved
EltrombopagThe serum concentration of Methotrexate can be increased when it is combined with Eltrombopag.Approved
EnalaprilThe serum concentration of Methotrexate can be increased when it is combined with Enalapril.Approved, Vet Approved
EnzalutamideThe serum concentration of Methotrexate can be increased when it is combined with Enzalutamide.Approved
EpirizoleThe serum concentration of Methotrexate can be increased when it is combined with Epirizole.Approved
ErgonovineThe serum concentration of Methotrexate can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Methotrexate can be increased when it is combined with Ergotamine.Approved
ErythromycinThe serum concentration of Methotrexate can be decreased when it is combined with Erythromycin.Approved, Vet Approved
EsomeprazoleThe serum concentration of Methotrexate can be increased when it is combined with Esomeprazole.Approved, Investigational
EstramustineThe serum concentration of Methotrexate can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Methotrexate can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Methotrexate can be decreased when it is combined with Estrone.Approved
Etacrynic acidThe therapeutic efficacy of Etacrynic acid can be decreased when used in combination with Methotrexate.Approved
EtanerceptThe serum concentration of Methotrexate can be increased when it is combined with Etanercept.Approved, Investigational
EtodolacThe serum concentration of Methotrexate can be increased when it is combined with Etodolac.Approved, Investigational, Vet Approved
EtofenamateThe serum concentration of Methotrexate can be increased when it is combined with Etofenamate.Approved
EtoposideThe serum concentration of Methotrexate can be increased when it is combined with Etoposide.Approved
EtoricoxibThe serum concentration of Methotrexate can be increased when it is combined with Etoricoxib.Approved, Investigational
EtravirineThe serum concentration of Methotrexate can be increased when it is combined with Etravirine.Approved
Evening primrose oilThe serum concentration of Methotrexate can be increased when it is combined with Evening primrose oil.Approved
exisulindThe serum concentration of Methotrexate can be increased when it is combined with exisulind.Investigational
FelodipineThe serum concentration of Methotrexate can be increased when it is combined with Felodipine.Approved, Investigational
FenbufenThe serum concentration of Methotrexate can be increased when it is combined with Fenbufen.Approved
FenoprofenThe serum concentration of Methotrexate can be increased when it is combined with Fenoprofen.Approved
FentanylThe serum concentration of Methotrexate can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Methotrexate can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Methotrexate can be increased when it is combined with Fidaxomicin.Approved
FingolimodMethotrexate may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FloctafenineThe serum concentration of Methotrexate can be increased when it is combined with Floctafenine.Approved, Withdrawn
FlucloxacillinThe serum concentration of Methotrexate can be increased when it is combined with Flucloxacillin.Approved
FluconazoleThe serum concentration of Methotrexate can be increased when it is combined with Fluconazole.Approved
FlunixinThe serum concentration of Methotrexate can be increased when it is combined with Flunixin.Vet Approved
FluoxetineThe serum concentration of Methotrexate can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Methotrexate can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Methotrexate can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Methotrexate can be increased when it is combined with Flurazepam.Approved, Illicit
FlurbiprofenThe serum concentration of Methotrexate can be increased when it is combined with Flurbiprofen.Approved, Investigational
FluvoxamineThe serum concentration of Methotrexate can be increased when it is combined with Fluvoxamine.Approved, Investigational
FoscarnetFoscarnet may increase the nephrotoxic activities of Methotrexate.Approved
FosphenytoinThe serum concentration of Fosphenytoin can be decreased when it is combined with Methotrexate.Approved
FurosemideThe therapeutic efficacy of Furosemide can be decreased when used in combination with Methotrexate.Approved, Vet Approved
G17DTThe risk or severity of adverse effects can be increased when Methotrexate is combined with G17DT.Investigational
GefitinibThe serum concentration of Methotrexate can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Methotrexate can be increased when it is combined with Genistein.Investigational
GI-5005The risk or severity of adverse effects can be increased when Methotrexate is combined with GI-5005.Investigational
GlyburideThe serum concentration of Methotrexate can be increased when it is combined with Glyburide.Approved
GlycerolThe serum concentration of Methotrexate can be increased when it is combined with Glycerol.Experimental
Gramicidin DThe serum concentration of Methotrexate can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Methotrexate can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Methotrexate can be increased when it is combined with Haloperidol.Approved
HigenamineThe serum concentration of Methotrexate can be increased when it is combined with Higenamine.Investigational
HMPL-004The serum concentration of Methotrexate can be increased when it is combined with HMPL-004.Investigational
HydrocortisoneThe serum concentration of Methotrexate can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IbuprofenThe serum concentration of Methotrexate can be increased when it is combined with Ibuprofen.Approved
IbuproxamThe serum concentration of Methotrexate can be increased when it is combined with Ibuproxam.Withdrawn
IcatibantThe serum concentration of Methotrexate can be increased when it is combined with Icatibant.Approved
IdelalisibThe serum concentration of Methotrexate can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Methotrexate can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Methotrexate can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Methotrexate can be decreased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Methotrexate can be increased when it is combined with Indomethacin.Approved, Investigational
IndoprofenThe serum concentration of Methotrexate can be increased when it is combined with Indoprofen.Withdrawn
INGN 201The risk or severity of adverse effects can be increased when Methotrexate is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Methotrexate is combined with INGN 225.Investigational
IsavuconazoniumThe serum concentration of Methotrexate can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsoxicamThe serum concentration of Methotrexate can be increased when it is combined with Isoxicam.Withdrawn
ItraconazoleThe serum concentration of Methotrexate can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Methotrexate can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Methotrexate can be increased when it is combined with Ivermectin.Approved, Vet Approved
KebuzoneThe serum concentration of Methotrexate can be increased when it is combined with Kebuzone.Experimental
KetamineThe serum concentration of Methotrexate can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe serum concentration of Methotrexate can be increased when it is combined with Ketoconazole.Approved, Investigational
KetoprofenThe serum concentration of Methotrexate can be increased when it is combined with Ketoprofen.Approved, Vet Approved
KetorolacThe serum concentration of Methotrexate can be increased when it is combined with Ketorolac.Approved
LansoprazoleThe serum concentration of Methotrexate can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Methotrexate can be increased when it is combined with Lapatinib.Approved, Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Methotrexate is combined with Leflunomide.Approved, Investigational
LevofloxacinThe serum concentration of Methotrexate can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Methotrexate can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Methotrexate can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Methotrexate can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Methotrexate can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Methotrexate can be increased when it is combined with Lisinopril.Approved, Investigational
LisofyllineThe serum concentration of Methotrexate can be increased when it is combined with Lisofylline.Investigational
LomitapideThe serum concentration of Methotrexate can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Methotrexate can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Methotrexate can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Methotrexate can be increased when it is combined with Loratadine.Approved
LornoxicamThe serum concentration of Methotrexate can be increased when it is combined with Lornoxicam.Approved
LosartanThe serum concentration of Methotrexate can be increased when it is combined with Losartan.Approved
LovastatinThe serum concentration of Methotrexate can be increased when it is combined with Lovastatin.Approved, Investigational
LoxoprofenThe serum concentration of Methotrexate can be increased when it is combined with Loxoprofen.Approved
LumacaftorThe serum concentration of Methotrexate can be decreased when it is combined with Lumacaftor.Approved
LumiracoxibThe serum concentration of Methotrexate can be increased when it is combined with Lumiracoxib.Approved, Investigational
Magnesium salicylateThe serum concentration of Methotrexate can be increased when it is combined with Magnesium salicylate.Approved
MaprotilineThe serum concentration of Methotrexate can be increased when it is combined with Maprotiline.Approved
MasoprocolThe serum concentration of Methotrexate can be increased when it is combined with Masoprocol.Approved
MebendazoleThe serum concentration of Methotrexate can be increased when it is combined with Mebendazole.Approved, Vet Approved
Meclofenamic acidThe serum concentration of Methotrexate can be increased when it is combined with Meclofenamic acid.Approved, Vet Approved
Mefenamic acidThe serum concentration of Methotrexate can be increased when it is combined with Mefenamic acid.Approved
MefloquineThe serum concentration of Methotrexate can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Methotrexate can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeloxicamThe serum concentration of Methotrexate can be increased when it is combined with Meloxicam.Approved, Vet Approved
MeprobamateThe serum concentration of Methotrexate can be increased when it is combined with Meprobamate.Approved, Illicit
MesalazineThe serum concentration of Methotrexate can be increased when it is combined with Mesalazine.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Methotrexate is combined with Metamizole.Withdrawn
MethadoneThe serum concentration of Methotrexate can be increased when it is combined with Methadone.Approved
MeticillinThe serum concentration of Methotrexate can be increased when it is combined with Meticillin.Approved
MetoprololThe serum concentration of Methotrexate can be increased when it is combined with Metoprolol.Approved, Investigational
MezlocillinThe serum concentration of Methotrexate can be increased when it is combined with Mezlocillin.Approved
MibefradilThe serum concentration of Methotrexate can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Methotrexate can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Methotrexate can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Methotrexate can be decreased when it is combined with Mifepristone.Approved, Investigational
MipomersenMipomersen may increase the hepatotoxic activities of Methotrexate.Approved
MitomycinThe serum concentration of Methotrexate can be increased when it is combined with Mitomycin.Approved
MitoxantroneThe serum concentration of Methotrexate can be decreased when it is combined with Mitoxantrone.Approved, Investigational
MizoribineThe serum concentration of Methotrexate can be increased when it is combined with Mizoribine.Investigational
MorphineThe serum concentration of Methotrexate can be increased when it is combined with Morphine.Approved, Investigational
Mycophenolate mofetilThe serum concentration of Methotrexate can be increased when it is combined with Mycophenolate mofetil.Approved, Investigational
Mycophenolic acidThe serum concentration of Methotrexate can be increased when it is combined with Mycophenolic acid.Approved
NabumetoneThe serum concentration of Methotrexate can be increased when it is combined with Nabumetone.Approved
NafamostatThe serum concentration of Methotrexate can be increased when it is combined with Nafamostat.Investigational
NafcillinThe serum concentration of Methotrexate can be increased when it is combined with Nafcillin.Approved
NaftifineThe serum concentration of Methotrexate can be increased when it is combined with Naftifine.Approved
NaltrexoneThe serum concentration of Methotrexate can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaproxenThe serum concentration of Methotrexate can be increased when it is combined with Naproxen.Approved, Vet Approved
NaringeninThe serum concentration of Methotrexate can be increased when it is combined with Naringenin.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Methotrexate is combined with Natalizumab.Approved, Investigational
NCX 4016The serum concentration of Methotrexate can be increased when it is combined with NCX 4016.Investigational
NefazodoneThe serum concentration of Methotrexate can be decreased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Methotrexate can be decreased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Methotrexate can be increased when it is combined with Neostigmine.Approved, Vet Approved
NepafenacThe serum concentration of Methotrexate can be increased when it is combined with Nepafenac.Approved
NicardipineThe serum concentration of Methotrexate can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Methotrexate can be decreased when it is combined with Nifedipine.Approved
Niflumic AcidThe serum concentration of Methotrexate can be increased when it is combined with Niflumic Acid.Approved
NilotinibThe serum concentration of Methotrexate can be increased when it is combined with Nilotinib.Approved, Investigational
NimesulideThe serum concentration of Methotrexate can be increased when it is combined with Nimesulide.Approved, Withdrawn
NisoldipineThe serum concentration of Methotrexate can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Methotrexate can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Methotrexate can be increased when it is combined with Nitrendipine.Approved
NitroaspirinThe serum concentration of Methotrexate can be increased when it is combined with Nitroaspirin.Investigational
NorethisteroneThe serum concentration of Methotrexate can be decreased when it is combined with Norethisterone.Approved
OlopatadineThe serum concentration of Methotrexate can be increased when it is combined with Olopatadine.Approved
OlsalazineThe serum concentration of Methotrexate can be increased when it is combined with Olsalazine.Approved
OmeprazoleThe serum concentration of Methotrexate can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OrgoteinThe serum concentration of Methotrexate can be increased when it is combined with Orgotein.Vet Approved
OuabainOuabain may decrease the cardiotoxic activities of Methotrexate.Approved
OxacillinThe serum concentration of Methotrexate can be increased when it is combined with Oxacillin.Approved
OxaprozinThe serum concentration of Methotrexate can be increased when it is combined with Oxaprozin.Approved
OxyphenbutazoneThe serum concentration of Methotrexate can be increased when it is combined with Oxyphenbutazone.Withdrawn
P-NitrophenolThe serum concentration of Methotrexate can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Methotrexate.Approved, Vet Approved
Palmitic AcidThe serum concentration of Methotrexate can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Methotrexate can be increased when it is combined with Pantoprazole.Approved
ParecoxibThe serum concentration of Methotrexate can be increased when it is combined with Parecoxib.Approved
ParoxetineThe serum concentration of Methotrexate can be increased when it is combined with Paroxetine.Approved, Investigational
PerindoprilThe serum concentration of Methotrexate can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe serum concentration of Methotrexate can be decreased when it is combined with Phenobarbital.Approved
PhenoxymethylpenicillinThe serum concentration of Methotrexate can be increased when it is combined with Phenoxymethylpenicillin.Approved, Vet Approved
PhenylbutazoneThe serum concentration of Methotrexate can be increased when it is combined with Phenylbutazone.Approved, Vet Approved
PhenytoinThe serum concentration of Phenytoin can be decreased when it is combined with Methotrexate.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Methotrexate.Approved, Investigational
PimozideThe serum concentration of Methotrexate can be increased when it is combined with Pimozide.Approved
PiperacillinThe serum concentration of Methotrexate can be increased when it is combined with Piperacillin.Approved
PiretanideThe therapeutic efficacy of Piretanide can be decreased when used in combination with Methotrexate.Experimental
PirfenidoneThe serum concentration of Methotrexate can be increased when it is combined with Pirfenidone.Investigational
PiroxicamThe serum concentration of Methotrexate can be increased when it is combined with Piroxicam.Approved, Investigational
PivampicillinThe serum concentration of Methotrexate can be increased when it is combined with Pivampicillin.Approved
PivmecillinamThe serum concentration of Methotrexate can be increased when it is combined with Pivmecillinam.Approved
Platelet Activating FactorThe serum concentration of Methotrexate can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Methotrexate can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe serum concentration of Methotrexate can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Methotrexate can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Methotrexate can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Methotrexate can be increased when it is combined with Prednisone.Approved, Vet Approved
ProbenecidThe serum concentration of Methotrexate can be increased when it is combined with Probenecid.Approved
Procaine benzylpenicillinThe serum concentration of Methotrexate can be increased when it is combined with Procaine benzylpenicillin.Approved, Vet Approved
ProgesteroneThe serum concentration of Methotrexate can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Methotrexate can be increased when it is combined with Promethazine.Approved
PropacetamolThe serum concentration of Methotrexate can be increased when it is combined with Propacetamol.Approved
PropafenoneThe serum concentration of Methotrexate can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Methotrexate can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Methotrexate can be increased when it is combined with Protriptyline.Approved
PTC299The serum concentration of Methotrexate can be increased when it is combined with PTC299.Investigational
QuercetinThe serum concentration of Methotrexate can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Methotrexate can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Methotrexate can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Methotrexate can be increased when it is combined with Quinine.Approved
RabeprazoleThe serum concentration of Methotrexate can be increased when it is combined with Rabeprazole.Approved, Investigational
Rabies vaccineThe risk or severity of adverse effects can be increased when Methotrexate is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Methotrexate.Approved
RanitidineThe serum concentration of Methotrexate can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Methotrexate can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Methotrexate can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Methotrexate can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Methotrexate can be decreased when it is combined with Reserpine.Approved
ResveratrolThe serum concentration of Methotrexate can be increased when it is combined with Resveratrol.Experimental, Investigational
RifampicinThe serum concentration of Methotrexate can be decreased when it is combined with Rifampicin.Approved
RilpivirineThe serum concentration of Methotrexate can be increased when it is combined with Rilpivirine.Approved
RitonavirThe serum concentration of Methotrexate can be decreased when it is combined with Ritonavir.Approved, Investigational
RofecoxibThe serum concentration of Methotrexate can be increased when it is combined with Rofecoxib.Investigational, Withdrawn
RoflumilastRoflumilast may increase the immunosuppressive activities of Methotrexate.Approved
RolapitantThe serum concentration of Methotrexate can be increased when it is combined with Rolapitant.Approved
SalicylamideThe serum concentration of Methotrexate can be increased when it is combined with Salicylamide.Approved
Salicylic acidThe serum concentration of Methotrexate can be increased when it is combined with Salicylic acid.Approved, Vet Approved
SalsalateThe serum concentration of Methotrexate can be increased when it is combined with Salsalate.Approved
SapropterinThe serum concentration of Sapropterin can be decreased when it is combined with Methotrexate.Approved, Investigational
SaquinavirThe serum concentration of Methotrexate can be decreased when it is combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Methotrexate can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Methotrexate can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SeratrodastThe serum concentration of Methotrexate can be increased when it is combined with Seratrodast.Approved, Investigational
SertralineThe serum concentration of Methotrexate can be increased when it is combined with Sertraline.Approved
SimeprevirThe serum concentration of Methotrexate can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Methotrexate can be increased when it is combined with Simvastatin.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Methotrexate.Approved
SirolimusThe serum concentration of Methotrexate can be decreased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Methotrexate can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Methotrexate can be increased when it is combined with Spironolactone.Approved
SRP 299The risk or severity of adverse effects can be increased when Methotrexate is combined with SRP 299.Investigational
SRT501The serum concentration of Methotrexate can be increased when it is combined with SRT501.Investigational
St. John's WortThe serum concentration of Methotrexate can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Methotrexate can be increased when it is combined with Staurosporine.Experimental
StreptozocinThe serum concentration of Methotrexate can be decreased when it is combined with Streptozocin.Approved
SulbactamThe serum concentration of Methotrexate can be increased when it is combined with Sulbactam.Approved
SulfadiazineThe risk or severity of adverse effects can be increased when Sulfadiazine is combined with Methotrexate.Approved, Vet Approved
SulfamethoxazoleThe risk or severity of adverse effects can be increased when Sulfamethoxazole is combined with Methotrexate.Approved
SulfasalazineSulfasalazine may increase the hepatotoxic activities of Methotrexate.Approved
SulfinpyrazoneThe serum concentration of Methotrexate can be increased when it is combined with Sulfinpyrazone.Approved
SulfisoxazoleThe risk or severity of adverse effects can be increased when Sulfisoxazole is combined with Methotrexate.Approved, Vet Approved
SulindacThe serum concentration of Methotrexate can be increased when it is combined with Sulindac.Approved
SultamicillinThe serum concentration of Methotrexate can be increased when it is combined with Sultamicillin.Investigational
SumatriptanThe serum concentration of Methotrexate can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Methotrexate can be increased when it is combined with Sunitinib.Approved, Investigational
SuprofenThe serum concentration of Methotrexate can be increased when it is combined with Suprofen.Approved, Withdrawn
TacrineThe serum concentration of Methotrexate can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Methotrexate.Approved, Investigational
TacrolimusThe serum concentration of Methotrexate can be decreased when it is combined with Tacrolimus.Approved, Investigational
TAK-390MRThe serum concentration of Methotrexate can be increased when it is combined with TAK-390MR.Investigational
TamoxifenThe serum concentration of Methotrexate can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Methotrexate can be increased when it is combined with Taurocholic Acid.Experimental
TazobactamThe serum concentration of Methotrexate can be increased when it is combined with Tazobactam.Approved
TegafurThe risk or severity of adverse effects can be increased when Methotrexate is combined with Tegafur.Approved
TelmisartanThe serum concentration of Methotrexate can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Methotrexate can be increased when it is combined with Temsirolimus.Approved
TenoxicamThe serum concentration of Methotrexate can be increased when it is combined with Tenoxicam.Approved
TepoxalinThe serum concentration of Methotrexate can be increased when it is combined with Tepoxalin.Vet Approved
TerazosinThe serum concentration of Methotrexate can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Methotrexate can be increased when it is combined with Terfenadine.Withdrawn
TeriflunomideThe serum concentration of Methotrexate can be increased when it is combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Methotrexate can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Methotrexate can be increased when it is combined with Testosterone.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Methotrexate is combined with TG4010.Investigational
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Methotrexate.Approved
Tiaprofenic acidThe serum concentration of Methotrexate can be increased when it is combined with Tiaprofenic acid.Approved
TicagrelorThe serum concentration of Methotrexate can be increased when it is combined with Ticagrelor.Approved
TicarcillinThe serum concentration of Methotrexate can be increased when it is combined with Ticarcillin.Approved, Vet Approved
TinoridineThe serum concentration of Methotrexate can be increased when it is combined with Tinoridine.Investigational
TofacitinibMethotrexate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
Tolfenamic AcidThe serum concentration of Methotrexate can be increased when it is combined with Tolfenamic Acid.Approved
TolmetinThe serum concentration of Methotrexate can be increased when it is combined with Tolmetin.Approved
TolvaptanThe serum concentration of Methotrexate can be increased when it is combined with Tolvaptan.Approved
TorasemideThe therapeutic efficacy of Torasemide can be decreased when used in combination with Methotrexate.Approved
TranilastThe serum concentration of Methotrexate can be increased when it is combined with Tranilast.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Methotrexate.Approved, Investigational
TrazodoneThe serum concentration of Methotrexate can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Methotrexate can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Methotrexate can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe risk or severity of adverse effects can be increased when Trimethoprim is combined with Methotrexate.Approved, Vet Approved
TrimipramineThe serum concentration of Methotrexate can be increased when it is combined with Trimipramine.Approved
Trisalicylate-cholineThe serum concentration of Methotrexate can be increased when it is combined with Trisalicylate-choline.Approved
TroleandomycinThe serum concentration of Methotrexate can be increased when it is combined with Troleandomycin.Approved
ValdecoxibThe serum concentration of Methotrexate can be increased when it is combined with Valdecoxib.Investigational, Withdrawn
VenlafaxineThe serum concentration of Methotrexate can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Methotrexate can be decreased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Methotrexate can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Methotrexate can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Methotrexate can be increased when it is combined with Vinorelbine.Approved, Investigational
ZaltoprofenThe serum concentration of Methotrexate can be increased when it is combined with Zaltoprofen.Approved
ZileutonThe serum concentration of Methotrexate can be increased when it is combined with Zileuton.Approved, Investigational, Withdrawn
ZimelidineThe serum concentration of Methotrexate can be increased when it is combined with Zimelidine.Withdrawn
ZomepiracThe serum concentration of Methotrexate can be increased when it is combined with Zomepirac.Withdrawn
Food Interactions
  • Milk appears to reduce its absorption.
  • Take without regard to meals. Limit caffeine intake.
References
Synthesis Reference

DrugSyn.org

US2512572
General References
  1. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martin Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M: Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004 Feb 28;363(9410):675-81. [PubMed:15001324 ]
  2. Johnston A, Gudjonsson JE, Sigmundsdottir H, Ludviksson BR, Valdimarsson H: The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol. 2005 Feb;114(2):154-63. [PubMed:15639649 ]
External Links
ATC CodesL01BA01L04AX03
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelDownload (518 KB)
MSDSDownload (77 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8261
Blood Brain Barrier-0.9467
Caco-2 permeable-0.7754
P-glycoprotein substrateSubstrate0.8172
P-glycoprotein inhibitor INon-inhibitor0.7752
P-glycoprotein inhibitor IINon-inhibitor0.9879
Renal organic cation transporterNon-inhibitor0.8886
CYP450 2C9 substrateNon-substrate0.85
CYP450 2D6 substrateNon-substrate0.7968
CYP450 3A4 substrateSubstrate0.5177
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8333
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9739
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9517
BiodegradationNot ready biodegradable0.9741
Rat acute toxicity3.4955 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9564
hERG inhibition (predictor II)Non-inhibitor0.6958
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Abic ltd
  • Pharmacia and upjohn co
  • Hospira inc
  • App pharmaceuticals llc
  • Abraxis pharmaceutical products
  • Bedford laboratories div ben venue laboratories inc
  • Norbrook laboratories ltd
  • Pharmachemie usa inc
  • Bioniche pharma usa llc
  • Ebewe pharma ges mbh nfg kg
  • Pharmachemie bv
  • Bristol laboratories inc div bristol myers co
  • Bristol myers co
  • Bristol myers squibb
  • Barr laboratories inc
  • Dava pharmaceuticals inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
Packagers
Dosage forms
FormRouteStrength
InjectionIntra-arterial; Intramuscular; Intrathecal; Intravenous25 mg/mL
Injection, powder, lyophilized, for solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous1 g/1
Injection, solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous1 g/40mL
Injection, solutionIntra-arterial; Intramuscular; Intravenous25 mg/mL
TabletOral2.5 mg/1
TabletOral2.5 mg
LiquidIntravenous10 mg
LiquidIntravenous2.5 mg
LiquidIntravenous25 mg
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous15 mg
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous20 mg
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous7.5 mg
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous10 mg
SolutionIntra-arterial; Intramuscular; Intravenous25 mg
SolutionIntravenous25 mg
Injection, solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous25 mg/mL
Powder, for solutionIntramuscular; Intrathecal; Intravenous20 mg
LiquidIntramuscular; Intrathecal; Intravenous25 mg
LiquidIntramuscular; Intrathecal; Intravenous50 mg
LiquidIntra-arterial; Intramuscular; Intrathecal; Intravenous25 mg
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous25 mg
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous; Intraventricular25 mg
TabletOral10 mg
Powder, for solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous20 mg
SolutionIntra-arterial; Intramuscular; Intravenous10 mg
SolutionIntra-arterial; Intramuscular; Intravenous15 mg
SolutionIntra-arterial; Intramuscular; Intravenous20 mg
SolutionIntra-arterial; Intramuscular; Intravenous7.5 mg
SolutionSubcutaneous10 mg
SolutionSubcutaneous12.5 mg
SolutionSubcutaneous15 mg
SolutionSubcutaneous17.5 mg
SolutionSubcutaneous20 mg
SolutionSubcutaneous22.5 mg
SolutionSubcutaneous25 mg
SolutionSubcutaneous7.5 mg
Injection, solutionSubcutaneous10 mg
Injection, solutionSubcutaneous12.5 mg
Injection, solutionSubcutaneous15 mg
Injection, solutionSubcutaneous17.5 mg
Injection, solutionSubcutaneous20 mg
Injection, solutionSubcutaneous22.5 mg
Injection, solutionSubcutaneous25 mg
Injection, solutionSubcutaneous7.5 mg
Injection, solutionSubcutaneous10 mg/.4mL
Injection, solutionSubcutaneous12.5 mg/.4mL
Injection, solutionSubcutaneous15 mg/.4mL
Injection, solutionSubcutaneous17.5 mg/.4mL
Injection, solutionSubcutaneous22.5 mg/.4mL
Injection, solutionSubcutaneous25 mg/.4mL
Injection, solutionSubcutaneous7.5 mg/.4mL
Injection, solutionSubcutaneous10 mg/.2mL
Injection, solutionSubcutaneous12.5 mg/.25mL
Injection, solutionSubcutaneous15 mg/.3mL
Injection, solutionSubcutaneous17.5 mg/.35mL
Injection, solutionSubcutaneous20 mg/.4mL
Injection, solutionSubcutaneous22.5 mg/.45mL
Injection, solutionSubcutaneous25 mg/.5mL
Injection, solutionSubcutaneous27.5 mg/.55mL
Injection, solutionSubcutaneous30 mg/.6mL
Injection, solutionSubcutaneous7.5 mg/.15mL
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral15 mg/1
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral7.5 mg/1
Prices
Unit descriptionCostUnit
Methotrexate powder261.33USD g
Rheumatrex 8 2.5 mg tablet Disp Pack169.98USD disp
Rheumatrex 24 2.5 mg tablet Disp Pack129.06USD disp
Rheumatrex 20 2.5 mg tablet Disp Pack107.59USD disp
Rheumatrex 12 2.5 mg tablet Disp Pack63.65USD disp
Methotrexate Sodium 25 mg/ml (pf) Solution 40ml Vial58.99USD vial
Trexall 15 mg tablet25.98USD tablet
Methotrexate Sodium 25 mg/ml (pf) Solution 10ml Vial24.99USD vial
Trexall 10 mg tablet17.67USD tablet
Methotrexate Sodium 25 mg/ml Solution 1 Vial = 2ml15.11USD vial
Methotrexate Sodium 25 mg/ml (pf) Solution 2ml Vial14.99USD vial
Trexall 7.5 mg tablet12.99USD tablet
Rheumatrex 2.5 mg tablet11.23USD tablet
Trexall 5 mg tablet8.66USD tablet
Methotrexate Sod. (Preserved) 25 mg/ml8.38USD ml
Methotrexate Sod.(Unpreserved) 25 mg/ml4.56USD ml
Methotrexate 2.5 mg tablet2.71USD tablet
Methotrexate 10 mg Tablet2.58USD tablet
Ratio-Methotrexate Sodium 2.5 mg Tablet0.66USD tablet
Apo-Methotrexate 2.5 mg Tablet0.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6746429 No2000-04-122020-04-12Us
US7744582 No1999-08-102019-08-10Us
US7776015 No1999-08-102019-08-10Us
US8021335 No2006-10-042026-10-04Us
US8480631 No2010-03-192030-03-19Us
US8562564 No2006-01-242026-01-24Us
US8579865 No2010-03-192030-03-19Us
US8664231 No2009-06-012029-06-01Us
US8945063 No2010-03-192030-03-19Us
USRE44846 No1999-08-102019-08-10Us
USRE44847 No1999-08-102019-08-10Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point195 °CNot Available
water solubility2600 mg/LNot Available
logP-1.85HANSCH,C ET AL. (1995)
Caco2 permeability-5.92ADME Research, USCD
pKa4.7SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.171 mg/mLALOGPS
logP-0.91ALOGPS
logP-0.5ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)3.41ChemAxon
pKa (Strongest Basic)2.81ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area210.54 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity119.21 m3·mol-1ChemAxon
Polarizability44.54 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (10.1 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-0fai-6900000000-25b0e287457fb3845ef4View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as folic acids. These are heterocyclic compounds based on the 4-[(pteridin-6-ylmethyl)amino]benzoic acid skeleton conjugated with one or more L-glutamate units.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassPterins and derivatives
Direct ParentFolic acids
Alternative Parents
Substituents
  • Folic acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Aminobenzoic acid or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Benzoic acid or derivatives
  • Benzamide
  • Aminobenzamide
  • Substituted aniline
  • Dialkylarylamine
  • Benzoyl
  • Aralkylamine
  • Aniline
  • Aminopyrimidine
  • Amino fatty acid
  • Fatty acyl
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Pyrazine
  • Primary aromatic amine
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. Al-Rashood ST, Aboldahab IA, Nagi MN, Abouzeid LA, Abdel-Aziz AA, Abdel-Hamide SG, Youssef KM, Al-Obaid AM, El-Subbagh HI: Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs. Bioorg Med Chem. 2006 Dec 15;14(24):8608-21. Epub 2006 Sep 12. [PubMed:16971132 ]
  2. Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007 Mar;26(1):153-81. [PubMed:17333344 ]
  3. Bennett B, Langan P, Coates L, Mustyakimov M, Schoenborn B, Howell EE, Dealwis C: Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18493-8. Epub 2006 Nov 27. [PubMed:17130456 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  5. Totani K, Matsuo I, Ihara Y, Ito Y: High-mannose-type glycan modifications of dihydrofolate reductase using glycan-methotrexate conjugates. Bioorg Med Chem. 2006 Aug 1;14(15):5220-9. Epub 2006 May 2. [PubMed:16647263 ]
  6. Uga H, Kuramori C, Ohta A, Tsuboi Y, Tanaka H, Hatakeyama M, Yamaguchi Y, Takahashi T, Kizaki M, Handa H: A new mechanism of methotrexate action revealed by target screening with affinity beads. Mol Pharmacol. 2006 Nov;70(5):1832-9. Epub 2006 Aug 25. [PubMed:16936229 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xanthine dehydrogenase activity
Specific Function:
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyz...
Gene Name:
AOX1
Uniprot ID:
Q06278
Molecular Weight:
147916.735 Da
References
  1. Zientek M, Jiang Y, Youdim K, Obach RS: In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase. Drug Metab Dispos. 2010 Aug;38(8):1322-7. doi: 10.1124/dmd.110.033555. Epub 2010 May 5. [PubMed:20444863 ]
  2. Baggott JE, Morgan SL: Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. Arthritis Rheum. 2009 Aug;60(8):2257-61. doi: 10.1002/art.24685. [PubMed:19644884 ]
  3. Jordan CG, Rashidi MR, Laljee H, Clarke SE, Brown JE, Beedham C: Aldehyde oxidase-catalysed oxidation of methotrexate in the liver of guinea-pig, rabbit and man. J Pharm Pharmacol. 1999 Apr;51(4):411-8. [PubMed:10385213 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein complex binding
Specific Function:
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name:
MTHFR
Uniprot ID:
P42898
Molecular Weight:
74595.895 Da
References
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865 ]
  2. Kremer JM: Methotrexate pharmacogenomics. Ann Rheum Dis. 2006 Sep;65(9):1121-3. [PubMed:16905578 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Phosphogluconate dehydrogenase (decarboxylating) activity
Specific Function:
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Gene Name:
PGD
Uniprot ID:
P52209
Molecular Weight:
53139.56 Da
References
  1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. doi: 10.3109/14756360903257900. [PubMed:20235752 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Tetrahydrofolylpolyglutamate synthase activity
Specific Function:
Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstituted reduced folates are the preferred s...
Gene Name:
FPGS
Uniprot ID:
Q05932
Molecular Weight:
64608.53 Da
References
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Omega peptidase activity
Specific Function:
Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.
Gene Name:
GGH
Uniprot ID:
Q92820
Molecular Weight:
35964.045 Da
References
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
References
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Protein homodimerization activity
Specific Function:
Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).
Gene Name:
ATIC
Uniprot ID:
P31939
Molecular Weight:
64615.255 Da
References
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
no
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Warnecke A, Fichtner I, Sass G, Kratz F: Synthesis, cleavage profile, and antitumor efficacy of an albumin-binding prodrug of methotrexate that is cleaved by plasmin and cathepsin B. Arch Pharm (Weinheim). 2007 Aug;340(8):389-95. [PubMed:17628030 ]
  2. Xie WJ, Feng YP, Cao SL, Zhao YF: [Study of the interaction between methotrexate and bovine serum albumin by spectrometry]. Guang Pu Xue Yu Guang Pu Fen Xi. 2006 Oct;26(10):1876-9. [PubMed:17205742 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Organic anion transmembrane transporter activity
Specific Function:
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity).
Gene Name:
ABCC3
Uniprot ID:
O15438
Molecular Weight:
169341.14 Da
References
  1. Akita H, Suzuki H, Hirohashi T, Takikawa H, Sugiyama Y: Transport activity of human MRP3 expressed in Sf9 cells: comparative studies with rat MRP3. Pharm Res. 2002 Jan;19(1):34-41. [PubMed:11837698 ]
  2. Oleschuk CJ, Deeley RG, Cole SP: Substitution of Trp1242 of TM17 alters substrate specificity of human multidrug resistance protein 3. Am J Physiol Gastrointest Liver Physiol. 2003 Feb;284(2):G280-9. Epub 2002 Oct 9. [PubMed:12388190 ]
  3. Hirohashi T, Suzuki H, Sugiyama Y: Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3). J Biol Chem. 1999 May 21;274(21):15181-5. [PubMed:10329726 ]
  4. Zeng H, Liu G, Rea PA, Kruh GD: Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res. 2000 Sep 1;60(17):4779-84. [PubMed:10987286 ]
  5. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759 ]
  6. Paumi CM, Wright M, Townsend AJ, Morrow CS: Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-Delta(12,14)prostaglandin J2 in MCF7 breast cancer cells. Biochemistry. 2003 May 13;42(18):5429-37. [PubMed:12731885 ]
  7. Li T, Ito K, Horie T: Transport of fluorescein methotrexate by multidrug resistance-associated protein 3 in IEC-6 cells. Am J Physiol Gastrointest Liver Physiol. 2003 Sep;285(3):G602-10. [PubMed:12909565 ]
  8. Zehnpfennig B, Urbatsch IL, Galla HJ: Functional reconstitution of human ABCC3 into proteoliposomes reveals a transport mechanism with positive cooperativity. Biochemistry. 2009 May 26;48(20):4423-30. doi: 10.1021/bi9001908. [PubMed:19334674 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
May be an organic anion pump relevant to cellular detoxification.
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular Weight:
149525.33 Da
References
  1. Chen ZS, Lee K, Kruh GD: Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J Biol Chem. 2001 Sep 7;276(36):33747-54. Epub 2001 Jul 10. [PubMed:11447229 ]
  2. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. [PubMed:12883481 ]
  3. Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [PubMed:14643890 ]
  4. van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG: The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol. 2002 Mar;13(3):595-603. [PubMed:11856762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J: Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta. 1997 May 22;1326(1):12-22. [PubMed:9188796 ]
  2. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759 ]
  3. Paumi CM, Wright M, Townsend AJ, Morrow CS: Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-Delta(12,14)prostaglandin J2 in MCF7 breast cancer cells. Biochemistry. 2003 May 13;42(18):5429-37. [PubMed:12731885 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Lu R, Chan BS, Schuster VL: Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2 Pt 2):F295-303. [PubMed:9950961 ]
  2. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [PubMed:9880528 ]
  3. Uwai Y, Okuda M, Takami K, Hashimoto Y, Inui K: Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Lett. 1998 Nov 6;438(3):321-4. [PubMed:9827570 ]
  4. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730 ]
  5. Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H: Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem. 1997 Jul 25;272(30):18526-9. [PubMed:9228014 ]
  6. Uwai Y, Iwamoto K: Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9. [PubMed:20460822 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name:
ABCC10
Uniprot ID:
Q5T3U5
Molecular Weight:
161627.375 Da
References
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [PubMed:12527806 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [PubMed:14762099 ]
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140 ]
  3. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [PubMed:11306713 ]
  4. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730 ]
  5. Uwai Y, Iwamoto K: Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9. [PubMed:20460822 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Han YH, Kato Y, Haramura M, Ohta M, Matsuoka H, Sugiyama Y: Physicochemical parameters responsible for the affinity of methotrexate analogs for rat canalicular multispecific organic anion transporter (cMOAT/MRP2). Pharm Res. 2001 May;18(5):579-86. [PubMed:11465411 ]
  2. Masuda M, I'izuka Y, Yamazaki M, Nishigaki R, Kato Y, Ni'inuma K, Suzuki H, Sugiyama Y: Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats. Cancer Res. 1997 Aug 15;57(16):3506-10. [PubMed:9270020 ]
  3. Hooijberg JH, Broxterman HJ, Kool M, Assaraf YG, Peters GJ, Noordhuis P, Scheper RJ, Borst P, Pinedo HM, Jansen G: Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res. 1999 Jun 1;59(11):2532-5. [PubMed:10363967 ]
  4. Bakos E, Evers R, Sinko E, Varadi A, Borst P, Sarkadi B: Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol. 2000 Apr;57(4):760-8. [PubMed:10727523 ]
  5. Chen C, Scott D, Hanson E, Franco J, Berryman E, Volberg M, Liu X: Impact of Mrp2 on the biliary excretion and intestinal absorption of furosemide, probenecid, and methotrexate using Eisai hyperbilirubinemic rats. Pharm Res. 2003 Jan;20(1):31-7. [PubMed:12608533 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Norris MD, De Graaf D, Haber M, Kavallaris M, Madafiglio J, Gilbert J, Kwan E, Stewart BW, Mechetner EB, Gudkov AV, Roninson IB: Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate. Int J Cancer. 1996 Mar 1;65(5):613-9. [PubMed:8598312 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibited by the grapefruit juice component naringin.
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular Weight:
74144.105 Da
References
  1. Cattori V, van Montfoort JE, Stieger B, Landmann L, Meijer DK, Winterhalter KH, Meier PJ, Hagenbuch B: Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95. [PubMed:11713643 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Symporter activity
Specific Function:
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bod...
Gene Name:
SLC16A1
Uniprot ID:
P53985
Molecular Weight:
53943.685 Da
References
  1. Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S, Tsuji A: Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol. 1999 Oct;51(10):1113-21. [PubMed:10579682 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Purine nucleotide transmembrane transporter activity
Specific Function:
Participates in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides. Enhances the cellular extrusion of cAMP and cGMP. Stimulates the ATP-dependent uptake of a range of physiological and synthetic lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates such as dehydroepiandrosterone 3-sulfate...
Gene Name:
ABCC11
Uniprot ID:
Q96J66
Molecular Weight:
154299.625 Da
References
  1. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. [PubMed:15537867 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
References
  1. Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R, Adachi H, Fujiwara K, Okabe M, Suzuki T, Nunoki K, Sato E, Kakyo M, Nishio T, Sugita J, Asano N, Tanemoto M, Seki M, Date F, Ono K, Kondo Y, Shiiba K, Suzuki M, Ohtani H, Shimosegawa T, Iinuma K, Nagura H, Ito S, Matsuno S: LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99. [PubMed:11375950 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular Weight:
59970.945 Da
References
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Thyroid hormone transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol, estrone-3-sulfate and sulfobromophthalein (BSP) are transported with much lower efficiency. May play a signifiant role in regulating T4 flux into and out of the brain (By similarity).
Gene Name:
SLCO1C1
Uniprot ID:
Q9NYB5
Molecular Weight:
78695.625 Da
References
  1. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [PubMed:12351693 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate (PubMed:10873595). Mediates transport of prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123 and vasopressin, but not DPDPE (a derivative of enkephalin lacking an N-terminal tyrosine residue), estrone-3-sulfate, taurocholate, digoxin nor DHEAS (PubMed:16971491).
Gene Name:
SLCO3A1
Uniprot ID:
Q9UIG8
Molecular Weight:
76552.135 Da
References
  1. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. [PubMed:14631946 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y: ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7. [PubMed:12682043 ]
  2. Breedveld P, Zelcer N, Pluim D, Sonmezer O, Tibben MM, Beijnen JH, Schinkel AH, van Tellingen O, Borst P, Schellens JH: Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004 Aug 15;64(16):5804-11. [PubMed:15313923 ]
  3. Mitomo H, Kato R, Ito A, Kasamatsu S, Ikegami Y, Kii I, Kudo A, Kobatake E, Sumino Y, Ishikawa T: A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport. Biochem J. 2003 Aug 1;373(Pt 3):767-74. [PubMed:12741957 ]
  4. Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. [PubMed:12874005 ]
  5. Volk EL, Schneider E: Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43. [PubMed:14500392 ]
  6. Suzuki K, Doki K, Homma M, Tamaki H, Hori S, Ohtani H, Sawada Y, Kohda Y: Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009 Jan;67(1):44-9. doi: 10.1111/j.1365-2125.2008.03303.x. Epub 2008 Nov 17. [PubMed:19076159 ]
  7. Hou YX, Li CZ, Palaniyandi K, Magtibay PM, Homolya L, Sarkadi B, Chang XB: Effects of putative catalytic base mutation E211Q on ABCG2-mediated methotrexate transport. Biochemistry. 2009 Sep 29;48(38):9122-31. doi: 10.1021/bi900675v. [PubMed:19691360 ]
  8. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995 ]
  9. Dai CL, Liang YJ, Wang YS, Tiwari AK, Yan YY, Wang F, Chen ZS, Tong XZ, Fu LW: Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18. [PubMed:19232821 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Sun W, Wu RR, van Poelje PD, Erion MD: Isolation of a family of organic anion transporters from human liver and kidney. Biochem Biophys Res Commun. 2001 May 4;283(2):417-22. [PubMed:11327718 ]
  2. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. [PubMed:9650585 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R, Adachi H, Fujiwara K, Okabe M, Suzuki T, Nunoki K, Sato E, Kakyo M, Nishio T, Sugita J, Asano N, Tanemoto M, Seki M, Date F, Ono K, Kondo Y, Shiiba K, Suzuki M, Ohtani H, Shimosegawa T, Iinuma K, Nagura H, Ito S, Matsuno S: LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99. [PubMed:11375950 ]
  2. van de Steeg E, van der Kruijssen CM, Wagenaar E, Burggraaff JE, Mesman E, Kenworthy KE, Schinkel AH: Methotrexate pharmacokinetics in transgenic mice with liver-specific expression of human organic anion-transporting polypeptide 1B1 (SLCO1B1). Drug Metab Dispos. 2009 Feb;37(2):277-81. doi: 10.1124/dmd.108.024315. Epub 2008 Nov 20. [PubMed:19022939 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Methotrexate transporter activity
Specific Function:
Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. The iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron. Shows a higher affinity for folate than heme.
Gene Name:
SLC46A1
Uniprot ID:
Q96NT5
Molecular Weight:
49770.04 Da
References
  1. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H: Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. Epub 2007 May 2. [PubMed:17475902 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ouabain. Involved in the uptake of the dipeptidyl peptidase-4 inhibitor sitagliptin and hence may play a role in its transport into and out of renal proximal tubule cells. May be involved in the first...
Gene Name:
SLCO4C1
Uniprot ID:
Q6ZQN7
Molecular Weight:
78947.525 Da
References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [PubMed:14993604 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Reduced folate carrier activity
Specific Function:
Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely the folate receptor, the folate transporter, and a V-type H(+)-pump.
Gene Name:
SLC19A1
Uniprot ID:
P41440
Molecular Weight:
64867.62 Da
References
  1. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID: Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. 2006 Dec 1;127(5):917-28. [PubMed:17129779 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Receptor activity
Specific Function:
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release. Required for norma...
Gene Name:
FOLR1
Uniprot ID:
P15328
Molecular Weight:
29818.94 Da
References
  1. Sharma S, Das M, Kumar A, Marwaha V, Shankar S, Aneja R, Grover R, Arya V, Dhir V, Gupta R, Kumar U, Juyal RC, B K T: Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians. Pharmacogenet Genomics. 2008 Dec;18(12):1041-9. [PubMed:19093297 ]
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Drug created on June 13, 2005 07:24 / Updated on December 09, 2016 02:40