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Identification
NameMethotrexate
Accession NumberDB00563  (APRD00353)
TypeSmall Molecule
GroupsApproved
Description

An 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
SynonymLanguageCode
4-amino-10-methylfolic acidNot AvailableNot Available
4-amino-N(10)-Methylpteroylglutamic acidNot AvailableNot Available
AmethopterinNot AvailableNot Available
EmtexateNot AvailableNot Available
LedertrexateNot AvailableNot Available
MethotrexatGermanINN
MéthotrexateFrenchINN
MethotrexatumLatinINN
MetotrexatoSpanishINN
MTXNot AvailableNot Available
N-[4-[[(2,4-Diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acidNot AvailableNot Available
RheumatrexNot AvailableNot Available
TrexallNot AvailableNot Available
Salts
Name/CAS Structure Properties
Methotrexate Sodium
Thumb
  • InChI Key: DASQOOZCTWOQPA-GXKRWWSZSA-L
  • Monoisotopic Mass: 498.13520514
  • Average Mass: 498.4029
DBSALT000115
Brand names
NameCompany
AbitrexateTeva
AlltrexNaprod
ArtraitTRB
AtrexelSchering-Plough
BendatrexatBendalis
CarditrexCadila
DermotrexEast West
EbetrexEbewe
EmtexateNot Available
LedertrexateBiodim
MaxtrexPfizer
MeisushengHospira
MexateCadila HC
OtrexupNot Available
RheumatrexWyeth KK
TrexallBarr
TrexanAtafarm
ZexateDabur Pharma
Brand mixturesNot Available
Categories
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
Mass Specshow(10.1 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzamides
Direct parentHippuric Acid Derivatives
Alternative parentsN-acyl-alpha Amino Acids; Pteridines and Derivatives; Benzoyl Derivatives; Aminopyrimidines and Derivatives; Amino Fatty Acids; Primary Aromatic Amines; Dicarboxylic Acids and Derivatives; Pyrazines; Tertiary Amines; Polyols; Secondary Carboxylic Acid Amides; Enolates; Carboxylic Acids; Polyamines
Substituentsalpha-amino acid or derivative; pteridine; benzoyl; aminopyrimidine; pyrimidine; pyrazine; dicarboxylic acid derivative; primary aromatic amine; tertiary amine; polyol; secondary carboxylic acid amide; carboxamide group; polyamine; enolate; carboxylic acid; carboxylic acid derivative; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the hippuric acid derivatives. These are compounds containing an hippuric acid or a derivative, with a structure characterized the presence of a benzoyl group linked to the N-terminal of a glycine.
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.
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.
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
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8261
Blood Brain Barrier - 0.9467
Caco-2 permeable - 0.7754
P-glycoprotein substrate Substrate 0.8172
P-glycoprotein inhibitor I Non-inhibitor 0.7752
P-glycoprotein inhibitor II Non-inhibitor 0.9879
Renal organic cation transporter Non-inhibitor 0.8886
CYP450 2C9 substrate Non-substrate 0.85
CYP450 2D6 substrate Non-substrate 0.7968
CYP450 3A4 substrate Substrate 0.5177
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8333
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9739
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9517
Biodegradation Not ready biodegradable 0.9741
Rat acute toxicity 3.4955 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9564
hERG inhibition (predictor II) Non-inhibitor 0.6958
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
Injection, powder, lyophilized, for solutionParenteral1 g
Injection, solutionParenteral25 mg/mL; 50 mg/2 mL; 100 mg/4 mL; 200 mg/8 mL; 250 mg/10 mL; 1 g/40 mL
TabletOral2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg
Prices
Unit descriptionCostUnit
Methotrexate powder261.33USDg
Rheumatrex 8 2.5 mg tablet Disp Pack169.98USDdisp
Rheumatrex 24 2.5 mg tablet Disp Pack129.06USDdisp
Rheumatrex 20 2.5 mg tablet Disp Pack107.59USDdisp
Rheumatrex 12 2.5 mg tablet Disp Pack63.65USDdisp
Methotrexate Sodium 25 mg/ml (pf) Solution 40ml Vial58.99USDvial
Trexall 15 mg tablet25.98USDtablet
Methotrexate Sodium 25 mg/ml (pf) Solution 10ml Vial24.99USDvial
Trexall 10 mg tablet17.67USDtablet
Methotrexate Sodium 25 mg/ml Solution 1 Vial = 2ml15.11USDvial
Methotrexate Sodium 25 mg/ml (pf) Solution 2ml Vial14.99USDvial
Trexall 7.5 mg tablet12.99USDtablet
Rheumatrex 2.5 mg tablet11.23USDtablet
Trexall 5 mg tablet8.66USDtablet
Methotrexate Sod. (Preserved) 25 mg/ml8.38USDml
Methotrexate Sod.(Unpreserved) 25 mg/ml4.56USDml
Methotrexate 2.5 mg tablet2.71USDtablet
Methotrexate 10 mg Tablet2.58USDtablet
Ratio-Methotrexate Sodium 2.5 mg Tablet0.66USDtablet
Apo-Methotrexate 2.5 mg Tablet0.66USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
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 Solubility0.171ALOGPS
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 FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra1D NMR
References
Synthesis Reference

DrugSyn.org

US2512572
General Reference
  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
  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
External Links
ResourceLink
KEGG DrugD00142
KEGG CompoundC01937
PubChem Compound126941
PubChem Substance46507678
ChemSpider112728
BindingDB18050
ChEBI6837
ChEMBLCHEMBL34259
Therapeutic Targets DatabaseDNC000933
PharmGKBPA450428
HETMTX
Drug Product Database2244798
RxListhttp://www.rxlist.com/cgi/generic/mtx.htm
Drugs.comhttp://www.drugs.com/methotrexate.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/met1257.shtml
WikipediaMethotrexate
ATC CodesL01BA01L04AX03
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelshow(518 KB)
MSDSshow(77 KB)
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid increases the effect and toxicity of methotrexate.
AcitretinAcitretin/etretinate increases the effect and toxicity of methotrexate
AmoxicillinThe penicillin increases the effect and toxicity of methotrexate
AmpicillinThe penicillin increases the effect and toxicity of methotrexate
BacampicillinThe penicillin increases the effect and toxicity of methotrexate
BenzylpenicillinThe penicillin increases the effect and toxicity of methotrexate
Bismuth SubsalicylateThe salicylate, bismuth subsalicylate, increases the effect and toxicity of methotrexate.
CarbenicillinThe penicillin increases the effect and toxicity of methotrexate
CholestyramineDecreased levels of methotrexate
CiprofloxacinCiprofloxacine may decrease the metabolism of methotrexate. Monitor for changes adverse effects of methotrexate if ciprofloxacin is initiated.
CisplatinCisplatin increases methotrexate toxicity
ClavulanateThe penicillin increases the effect and toxicity of methotrexate
CloxacillinThe penicillin increases the effect and toxicity of methotrexate
CyclosporineCyclosporine may increase the effect and toxicity of methotrexate.
DiclofenacThe NSAID, diclofenac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
DicloxacillinThe penicillin increases the effect and toxicity of methotrexate
DiflunisalThe NSAID, diflunisal, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
DigoxinThe antineoplasic agent decreases the effect of digoxin
DoxycyclineThe tetracycline, doxycycline, may increase methotrexate toxicity.
EltrombopagIncreases levels of Methotrexate via metabolism decrease. OATP transporter protein inhibition.
EthotoinThe antineoplasic agent decreases the effect of hydantoin
EtodolacThe NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
EtretinateAcitretin/etretinate increases the effect and toxicity of methotrexate
FenoprofenThe NSAID, fenoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
FlucloxacillinThe penicillin increases the effect and toxicity of methotrexate
FlurbiprofenThe NSAID, flurbiprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
FosphenytoinThe antineoplasic agent decreases the effect of hydantoin
HydroxychloroquineHydroxychloroquine increases the effect and toxicity of methotrexate
IbuprofenThe NSAID, ibuprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
IndomethacinThe NSAID, indomethacin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
KetoprofenThe NSAID, ketoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
KetorolacThe NSAID, ketorolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Magnesium salicylateThe salicylate, magnesium salicylate, increases the effect and toxicity of methotrexate.
Meclofenamic acidThe NSAID, meclofenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Mefenamic acidThe NSAID, mefenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
MephenytoinThe antineoplasic agent decreases the effect of hydantoin
Methicillin Acyl-SerineThe penicillin increases the effect and toxicity of methotrexate
MezlocillinThe penicillin increases the effect and toxicity of methotrexate
NabumetoneThe NSAID, nabumetone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
NafcillinThe penicillin increases the effect and toxicity of methotrexate
NaproxenThe NSAID, naproxen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
OmeprazoleOmeprazole increases the levels of methotrexate
OxaprozinThe NSAID, oxaprozin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Penicillin VThe penicillin increases the effect and toxicity of methotrexate
PhenylbutazoneThe NSAID, phenylbutazone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
PhenytoinThe antineoplasic agent decreases the effect of hydantoin
PiperacillinThe penicillin increases the effect and toxicity of methotrexate
PiroxicamThe NSAID, piroxicam, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
PivampicillinThe penicillin increases the effect and toxicity of methotrexate
ProbenecidProbenecid increases the effect and toxicity of methotrexate
ProcarbazineIncreased nephrotoxicity with this combination
RilonaceptRilonacept and methotrexate both increase immunosuppressive effects; combination may increase risk of myelosuppression.
RofecoxibRofecoxib increases the levels of methotrexate
Salicylate-sodiumThe salicylate, salicylate-sodium, increases the effect and toxicity of methotrexate.
SalsalateThe salicylate, salsalate, increases the effect and toxicity of methotrexate.
SulfacytineThe sulfamide increases the toxicity of methotrexate
SulfadiazineThe sulfamide increases the toxicity of methotrexate
SulfadimethoxineThe sulfamide increases the toxicity of methotrexate
SulfadoxineThe sulfamide increases the toxicity of methotrexate
SulfamerazineThe sulfamide increases the toxicity of methotrexate
SulfamethazineThe sulfamide increases the toxicity of methotrexate
SulfamethizoleThe sulfamide increases the toxicity of methotrexate
SulfamethoxazoleThe sulfamide increases the toxicity of methotrexate
SulfapyridineThe sulfamide increases the toxicity of methotrexate
SulfathiazoleThe sulfamide increases the toxicity of methotrexate
SulfisoxazoleThe sulfamide increases the toxicity of methotrexate
SulindacThe NSAID, sulindac, may decrease the clearance methotrexate. Consider alternate therapy, especially in patients receiving high antineoplastic doses of methotrexate. Otherwise, monitor for hematologic and renal toxicities.
TenoxicamTenoxicam may increase the serum concentration of Methotrexate by reducing renal tubular secretion of Methotrexate. Monitor for changes in Methotrexate therapeutic and adverse effects if Tenoxicam is initiated, discontinued or dose changed.
TetracyclineTetracycline may increase methotrexate toxicity.
Tiaprofenic acidTiaprofenic acid may decrease renal excretion of methotrexate. Consider alternate therapy or monitor for methotrexate toxicity.
TicarcillinThe penicillin increases the effect and toxicity of methotrexate
TolmetinTolmetin may decrease the renal excretion of Methotrexate. Alternate therapy should be considered. Otherwise, monitor for hemotologic and renal toxicities.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
TrimethoprimTrimethoprim may increase the adverse/toxic effects of Methotrexate (e.g. bone marrow suppression). Concomitant use should be avoided or closely monitored for Methotrexate toxicity.
Trisalicylate-cholineThe salicylate, trisalicylate-choline, increases the effect and toxicity of methotrexate.
Food Interactions
  • Milk appears to reduce its absorption.
  • Take without regard to meals. Limit caffeine intake.

Targets

1. Dihydrofolate reductase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Dihydrofolate reductase P00374 Details

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
  2. Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007 Mar;26(1):153-81. Pubmed
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  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

Enzymes

1. Methylenetetrahydrofolate reductase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Methylenetetrahydrofolate reductase P42898 Details

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
  2. Kremer JM: Methotrexate pharmacogenomics. Ann Rheum Dis. 2006 Sep;65(9):1121-3. Pubmed

2. Aldehyde oxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Aldehyde oxidase Q06278 Details

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. Epub 2010 May 5. Pubmed
  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. Pubmed
  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

3. 6-phosphogluconate dehydrogenase, decarboxylating

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
6-phosphogluconate dehydrogenase, decarboxylating P52209 Details

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 Mar 17. Pubmed
  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

4. Folylpolyglutamate synthase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Folylpolyglutamate synthase, mitochondrial Q05932 Details

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

5. Gamma-glutamyl hydrolase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Gamma-glutamyl hydrolase Q92820 Details

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

6. Dihydrofolate reductase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Dihydrofolate reductase P00374 Details

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

7. Thymidylate synthase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Thymidylate synthase P04818 Details

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

8. Bifunctional purine biosynthesis protein PURH

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Bifunctional purine biosynthesis protein PURH P31939 Details

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

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Serum albumin P02768 Details

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
  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

Transporters

1. Canalicular multispecific organic anion transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 2 O15438 Details

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
  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
  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
  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
  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
  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
  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
  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. Pubmed

2. Multidrug resistance-associated protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 4 O15439 Details

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
  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
  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
  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

3. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

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
  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
  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

4. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

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
  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
  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
  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
  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
  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

5. Multidrug resistance-associated protein 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 7 Q5T3U5 Details

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

6. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

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
  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
  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
  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
  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

7. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

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
  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
  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
  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
  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

8. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

9. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

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

10. Monocarboxylate transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Monocarboxylate transporter 1 P53985 Details

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

11. ATP-binding cassette sub-family C member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family C member 11 Q96J66 Details

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

12. Solute carrier organic anion transporter family member 1B3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B3 Q9NPD5 Details

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

13. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

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

14. Solute carrier organic anion transporter family member 1C1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1C1 Q9NYB5 Details

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

15. Solute carrier organic anion transporter family member 3A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 3A1 Q9UIG8 Details

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

16. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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
  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
  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
  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
  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
  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. Epub 2008 Nov 17. Pubmed
  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. Pubmed
  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. Epub 2009 Apr 11. Pubmed
  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. Epub 2009 Feb 18. Pubmed

17. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

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
  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

18. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

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
  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. Epub 2008 Nov 20. Pubmed

19. Proton-coupled folate transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Proton-coupled folate transporter Q96NT5 Details

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

20. Solute carrier organic anion transporter family member 4C1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 4C1 Q6ZQN7 Details

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

21. Folate transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Folate transporter 1 P41440 Details

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

22. Folate receptor alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Folate receptor alpha P15328 Details

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

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24