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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Methotrexate
- Accession Number
- DB00563 (APRD00353)
- Type
- Small Molecule
- Groups
- Approved
- 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.
- Structure
Structure for Methotrexate (DB00563)
- Synonyms
- 4-amino-10-methylfolic acid
- 4-amino-N(10)-methylpteroylglutamic acid
- Amethopterin
- Methotrexat
- Méthotrexate
- Methotrexatum
- Metotrexato
- MTX
- N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid
- External IDs
- CL 14377 / CL-14377 / EMT 25299 / EMT-25299 / NSC-740 / R 9985 / R-9985
- Product Ingredients
Ingredient UNII CAS InChI Key Methotrexate Sodium 3IG1E710ZN 7413-34-5 DASQOOZCTWOQPA-UHFFFAOYSA-L - Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Methotrexate Solution 25 mg/1mL Intra-arterial; Intramuscular; Intrathecal; Intravenous ThyMoorgan GmbH Pharmazir & Co. K.G 2018-01-05 Not applicable US 
Methotrexate Injection, solution 25 mg/1mL Subcutaneous Antares Pharma, Inc. 2017-12-01 2017-12-01 US Methotrexate Solution 25 mg/1mL Intra-arterial; Intramuscular; Intrathecal; Intravenous ThyMoorgan GmbH Pharmazir & Co. K.G 2017-10-10 Not applicable US Methotrexate Injection, solution 17.5 mg/0.7mL Subcutaneous Antares Pharma, Inc. 2017-12-01 2017-12-01 US Methotrexate Injection, solution 10 mg/0.4mL Subcutaneous Antares Pharma, Inc. 2017-12-01 2017-12-01 US Methotrexate Tablet 2.5 mg/1 Oral Remedy Repack 2017-02-15 Not applicable US Methotrexate Tablet 2.5 mg/1 Oral A-S Medication Solutions 1953-12-07 Not applicable US 
Methotrexate Tablet 2.5 mg/1 Oral Pd Rx Pharmaceuticals, Inc. 1953-12-07 2018-08-03 US Methotrexate Solution 25 mg/1mL Intra-arterial; Intramuscular; Intrathecal; Intravenous ThyMoorgan GmbH Pharmazir & Co. K.G 2018-01-05 Not applicable US Methotrexate Injection, solution 22.5 mg/0.9mL Subcutaneous Antares Pharma, Inc. 2017-12-01 2017-12-01 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Apo-methotrexate Tablet 2.5 mg Oral Pfizer 1999-09-17 Not applicable Canada 
Apo-methotrexate Tablet 2.5 mg Oral Apotex Corporation Not applicable Not applicable Canada Jamp-methotrexate Solution 25 mg Intra-arterial; Intramuscular; Intrathecal; Intravenous Jamp Pharma Corporation 2014-03-12 Not applicable Canada Methotrexate Injection, powder, lyophilized, for solution 1 g/1 Intra-arterial; Intramuscular; Intrathecal; Intravenous Fresenius Kabi USA, LLC 2000-01-22 Not applicable US Methotrexate Injection, solution 25 mg/1mL Intra-arterial; Intramuscular; Intrathecal; Intravenous Bedford Pharmaceuticals 1996-05-01 2012-10-31 US Methotrexate Injection 25 mg/1mL Intra-arterial; Intramuscular; Intrathecal; Intravenous Mylan Institutional 2017-10-03 Not applicable US Methotrexate Tablet 2.5 mg/1 Oral Teva Pharmaceuticals USA, Inc. 1990-11-01 Not applicable US 
Methotrexate Injection, powder, lyophilized, for solution 1 g/20mL Intra-arterial; Intramuscular; Intrathecal; Intravenous Bedford Pharmaceuticals 2005-09-06 2013-05-31 US Methotrexate Injection 25 mg/1mL Intra-arterial; Intramuscular; Intrathecal; Intravenous Pfizer Laboratories Div Pfizer Inc. 2012-03-30 2017-12-31 US Methotrexate Injection, solution 1 g/40mL Intra-arterial; Intramuscular; Intrathecal; Intravenous Mylan Institutional 2012-06-27 2018-05-07 US - International/Other Brands
- Abitrexate (Teva) / Alltrex (Naprod) / Artrait (TRB) / Atrexel (Schering-Plough) / Bendatrexat (Bendalis) / Carditrex (Cadila) / Dermotrex (East West) / Ebetrex (Ebewe) / Emtexate / Ledertrexate (Biodim) / Maxtrex (Pfizer) / Meisusheng (Hospira) / Mexate (Cadila HC) / Rheumatrex (Wyeth KK) / Trexan (Atafarm) / Zexate (Dabur Pharma)
- Categories
- Abortifacient Agents
- Abortifacient Agents, Nonsteroidal
- Aminopterin
- Antimetabolites
- Antimetabolites, Antineoplastic
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Biological Factors
- Cardiotoxic antineoplastic agents
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (moderate)
- Cytochrome P-450 CYP3A4 Substrates
- Dermatologicals
- Enzyme Inhibitors
- Folic Acid Analogues
- Folic Acid Antagonists
- Immunologic Factors
- Immunosuppressive Agents
- Myelosuppressive Agents
- Nephrotoxic agents
- Noxae
- Nucleic Acid Synthesis Inhibitors
- OAT3/SLC22A8 Inhibitors
- OAT3/SLC22A8 Substrates
- OATP1B1/SLCO1B1 Substrates
- P-glycoprotein/ABCB1 Substrates
- Pigments, Biological
- Pteridines
- Pterins
- Reproductive Control Agents
- Toxic Actions
- UNII
- YL5FZ2Y5U1
- CAS number
- 59-05-2
- Weight
- Average: 454.4393
Monoisotopic: 454.171315854 - Chemical Formula
- C20H22N8O5
- InChI Key
- FBOZXECLQNJBKD-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
- Indication
Methotrexate 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.
- Associated Conditions
- Acute Lymphocytic Leukemia (ALL)
- Acute Promyelocytic Leukemia (APL)
- Bladder Cancers
- Cancer, Breast
- Central Nervous System Lymphoma
- Choriocarcinoma
- Crohn's Disease (CD)
- Dermatomyositis
- Disseminated Sclerosis
- Extrauterine Pregnancy
- Graft Versus Host Disease (GVHD)
- Head and Neck Carcinoma
- Hydatidiform Mole
- Lung Cancer Small Cell Lung Cancer (SCLC)
- Meningeal leukemia
- Polymyositis
- Sarcoma, Osteogenic
- Soft Tissue Sarcoma (STS)
- Squamous Cell Carcinoma of Lung
- Systemic Lupus Erythematosus (SLE)
- Uveitis
- Active Pauciarticular juvenile rheumatoid arthritis
- Advanced Alibert-Bazin syndrome
- Advanced non-Hodgkin lymphoma
- Nonleukemic meningeal cancer
- Refractory Takayasu arteritis
- Severe Psoriasis
- Severe, active Rheumatoid arthritis
- Associated Therapies
- Pharmacodynamics
Methotrexate 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 action
Methotrexate 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.
Target Actions Organism ADihydrofolate reductase inhibitorHuman - Absorption
Oral 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 binding
50% 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.
- Route of elimination
Renal 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 life
Low 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.
- Toxicity
Symptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD50=43mg/kg(orally in rat).
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Methotrexate Action Pathway Drug action - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Canalicular multispecific organic anion transporter 1 ABCC2 IVS 23+56 (C;C) / (C;T) T allele ADR Directly Studied Patients with this genotype have increased risk of toxicity with methotrexate. Details Methylenetetrahydrofolate reductase --- (T;T) / (C;T) T allele ADR Directly Studied Patients with this genotype have increased risk of toxicity with methotrexate. Details
Interactions
- Drug Interactions
Drug Interaction (6R)-Folinic acid The therapeutic efficacy of Methotrexate can be decreased when used in combination with (6R)-Folinic acid. (6S)-5,6,7,8-tetrahydrofolate The therapeutic efficacy of Methotrexate can be decreased when used in combination with (6S)-5,6,7,8-tetrahydrofolate. (R)-warfarin The metabolism of (R)-warfarin can be increased when combined with Methotrexate. (S)-Warfarin The metabolism of (S)-Warfarin can be increased when combined with Methotrexate. 2-Methoxyethanol The risk or severity of adverse effects can be increased when Methotrexate is combined with 2-Methoxyethanol. 3-isobutyl-1-methyl-7H-xanthine The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Methotrexate. 3,5-diiodothyropropionic acid The metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Methotrexate. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be increased when combined with Methotrexate. 5-(2-methylpiperazine-1-sulfonyl)isoquinoline The risk or severity of adverse effects can be increased when 5-(2-methylpiperazine-1-sulfonyl)isoquinoline is combined with Methotrexate. 5-androstenedione The metabolism of 5-androstenedione can be increased when combined with Methotrexate. - Food Interactions
- Milk appears to reduce its absorption.
- Take without regard to meals. Limit caffeine intake.
References
- Synthesis Reference
- US2512572
- General References
- 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]
- 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
- Human Metabolome Database
- HMDB0014703
- KEGG Drug
- D00142
- KEGG Compound
- C01937
- PubChem Compound
- 126941
- PubChem Substance
- 46507678
- ChemSpider
- 112728
- BindingDB
- 66082
- ChEBI
- 44185
- ChEMBL
- CHEMBL34259
- Therapeutic Targets Database
- DNC000933
- PharmGKB
- PA450428
- HET
- MTX
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Methotrexate
- ATC Codes
- L01BA01 — Methotrexate
- L01BA — Folic acid analogues
- L01B — ANTIMETABOLITES
- L01 — ANTINEOPLASTIC AGENTS
- L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- PDB Entries
- 1ao8 / 1axw / 1d1g / 1ddr / 1dds / 1df7 / 1dhi / 1dhj / 1dls / 1dra … show 45 more
- FDA label
- Download (518 KB)
- MSDS
- Download (77 KB)
Clinical Trials
- Clinical Trials
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
- Apotheca Inc.
- APP Pharmaceuticals
- A-S Medication Solutions LLC
- Barr Pharmaceuticals
- Baxter International Inc.
- Bedford Labs
- Ben Venue Laboratories Inc.
- Bigmar Bioren Pharmaceuticals Sa
- Bryant Ranch Prepack
- DAVA Pharmaceuticals
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Duramed
- Ebewe Pharma
- Excella GmbH
- Gallipot
- Generamedix Inc.
- Hospira Inc.
- Intas Pharmaceuticals Ltd.
- Lake Erie Medical and Surgical Supply
- Major Pharmaceuticals
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- PD-Rx Pharmaceuticals Inc.
- Pharmedix
- Physicians Total Care Inc.
- Qualitest
- Rebel Distributors Corp.
- Remedy Repack
- Roxane Labs
- Spectrum Pharmaceuticals
- UDL Laboratories
- Wyeth Pharmaceuticals
- Dosage forms
Form Route Strength Injection Intra-arterial; Intramuscular; Intrathecal; Intravenous 25 mg/1mL Injection, powder, lyophilized, for solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 1 g/1 Injection, powder, lyophilized, for solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 1 g/20mL Injection, solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 1 g/40mL Injection, solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 25 mg/1mL Injection, solution Intra-arterial; Intramuscular; Intravenous 10 mg/1mL Injection, solution Intra-arterial; Intramuscular; Intravenous 25 mg/1mL Injection, solution Subcutaneous 10 mg/0.4mL Injection, solution Subcutaneous 15 mg/0.6mL Injection, solution Subcutaneous 17.5 mg/0.7mL Injection, solution Subcutaneous 20 mg/0.8mL Injection, solution Subcutaneous 22.5 mg/0.9mL Injection, solution Subcutaneous 25 mg/1mL Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 25 mg/1mL Liquid Intravenous 10 mg Liquid Intravenous 2.5 mg Liquid Intravenous 25 mg Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 25 mg Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous; Intraventricular 10 mg Solution Intra-arterial; Intramuscular; Intravenous 25 mg Solution Intravenous 25 mg Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 10 mg Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 15 mg Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 20 mg Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 7.5 mg Tablet Oral 2.5 mg/1 Powder, for solution Intramuscular; Intrathecal; Intravenous 20 mg Liquid Intramuscular; Intrathecal; Intravenous 25 mg Liquid Intramuscular; Intrathecal; Intravenous 50 mg Liquid Intra-arterial; Intramuscular; Intrathecal; Intravenous 25 mg Solution Intra-arterial; Intramuscular; Intrathecal; Intravenous; Intraventricular 25 mg Tablet Oral 10 mg Powder, for solution Intra-arterial; Intramuscular; Intrathecal; Intravenous 20 mg Solution Intra-arterial; Intramuscular; Intravenous 10 mg Solution Intra-arterial; Intramuscular; Intravenous 15 mg Solution Intra-arterial; Intramuscular; Intravenous 20 mg Solution Intra-arterial; Intramuscular; Intravenous 7.5 mg Solution Subcutaneous 10 mg Solution Subcutaneous 12.5 mg Solution Subcutaneous 15 mg Solution Subcutaneous 17.5 mg Solution Subcutaneous 20 mg Solution Subcutaneous 22.5 mg Solution Subcutaneous 25 mg Solution Subcutaneous 7.5 mg Injection, solution Subcutaneous 10 mg Injection, solution Subcutaneous 12.5 mg Injection, solution Subcutaneous 15 mg Injection, solution Subcutaneous 17.5 mg Injection, solution Subcutaneous 20 mg Injection, solution Subcutaneous 22.5 mg Injection, solution Subcutaneous 25 mg Injection, solution Subcutaneous 7.5 mg Injection, solution Subcutaneous 12.5 mg/0.4mL Injection, solution Subcutaneous 15 mg/0.4mL Injection, solution Subcutaneous 17.5 mg/0.4mL Injection, solution Subcutaneous 22.5 mg/0.4mL Injection, solution Subcutaneous 25 mg/0.4mL Injection, solution Subcutaneous 7.5 mg/0.4mL Injection, solution Subcutaneous 10 mg/0.2mL Injection, solution Subcutaneous 12.5 mg/0.25mL Injection, solution Subcutaneous 15 mg/0.3mL Injection, solution Subcutaneous 17.5 mg/0.35mL Injection, solution Subcutaneous 20 mg/0.4mL Injection, solution Subcutaneous 22.5 mg/0.45mL Injection, solution Subcutaneous 25 mg/0.5mL Injection, solution Subcutaneous 27.5 mg/0.55mL Injection, solution Subcutaneous 30 mg/0.6mL Injection, solution Subcutaneous 7.5 mg/0.15mL Tablet Oral 2.5 mg Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 15 mg/1 Tablet, film coated Oral 5 mg/1 Tablet, film coated Oral 7.5 mg/1 Solution Oral 2.5 mg/1mL - Prices
Unit description Cost Unit Methotrexate powder 261.33USD g Rheumatrex 8 2.5 mg tablet Disp Pack 169.98USD disp Rheumatrex 24 2.5 mg tablet Disp Pack 129.06USD disp Rheumatrex 20 2.5 mg tablet Disp Pack 107.59USD disp Rheumatrex 12 2.5 mg tablet Disp Pack 63.65USD disp Methotrexate Sodium 25 mg/ml (pf) Solution 40ml Vial 58.99USD vial Trexall 15 mg tablet 25.98USD tablet Methotrexate Sodium 25 mg/ml (pf) Solution 10ml Vial 24.99USD vial Trexall 10 mg tablet 17.67USD tablet Methotrexate Sodium 25 mg/ml Solution 1 Vial = 2ml 15.11USD vial Methotrexate Sodium 25 mg/ml (pf) Solution 2ml Vial 14.99USD vial Trexall 7.5 mg tablet 12.99USD tablet Rheumatrex 2.5 mg tablet 11.23USD tablet Trexall 5 mg tablet 8.66USD tablet Methotrexate Sod. (Preserved) 25 mg/ml 8.38USD ml Methotrexate Sod.(Unpreserved) 25 mg/ml 4.56USD ml Methotrexate 2.5 mg tablet 2.71USD tablet Methotrexate 10 mg Tablet 2.58USD tablet Ratio-Methotrexate Sodium 2.5 mg Tablet 0.66USD tablet Apo-Methotrexate 2.5 mg Tablet 0.66USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) US8480631 No 2010-03-19 2030-03-19 US USRE44847 No 1999-08-10 2019-08-10 US US8579865 No 2010-03-19 2030-03-19 US US8945063 No 2010-03-19 2030-03-19 US USRE44846 No 1999-08-10 2019-08-10 US US8021335 No 2006-10-04 2026-10-04 US US6746429 No 2000-04-12 2020-04-12 US US8562564 No 2006-01-24 2026-01-24 US US7744582 No 1999-08-10 2019-08-10 US US7776015 No 1999-08-10 2019-08-10 US US8664231 No 2009-06-01 2029-06-01 US US9533102 No 2006-01-24 2026-01-24 US US9629959 No 2006-01-24 2026-01-24 US US9421333 No 2010-03-19 2030-03-19 US US9259427 No 2013-01-02 2033-01-02 US US9855215 No 2013-01-02 2033-01-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 195 °C Not Available water solubility 2600 mg/L Not Available logP -1.85 HANSCH,C ET AL. (1995) Caco2 permeability -5.92 ADME Research, USCD pKa 4.7 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.171 mg/mL ALOGPS logP -0.91 ALOGPS logP -0.5 ChemAxon logS -3.4 ALOGPS pKa (Strongest Acidic) 3.41 ChemAxon pKa (Strongest Basic) 2.81 ChemAxon Physiological Charge -2 ChemAxon Hydrogen Acceptor Count 12 ChemAxon Hydrogen Donor Count 5 ChemAxon Polar Surface Area 210.54 Å2 ChemAxon Rotatable Bond Count 9 ChemAxon Refractivity 119.21 m3·mol-1 ChemAxon Polarizability 44.54 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - 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 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Download (10.1 KB)
- Spectra
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Glutamic acid and derivatives
- Alternative Parents
- N-acyl-alpha amino acids / Hippuric acids / Pteridines and derivatives / Aminobenzamides / Aniline and substituted anilines / Dialkylarylamines / Benzoyl derivatives / Aminopyrimidines and derivatives / Aralkylamines / Pyrazines show 11 more
- Substituents
- Glutamic acid or derivatives / Hippuric acid or derivatives / Hippuric acid / N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / Aminobenzamide / Aminobenzoic acid or derivatives / Pteridine / Benzamide / Benzoic acid or derivatives show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monocarboxylic acid amide, dicarboxylic acid, pteridines (CHEBI:44185)
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 pre...
- Gene Name
- DHFR
- Uniprot ID
- P00374
- Uniprot Name
- Dihydrofolate reductase
- Molecular Weight
- 21452.61 Da
References
- 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]
- Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007 Mar;26(1):153-81. [PubMed:17333344]
- 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]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- 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]
- 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
- 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 pre...
- Gene Name
- DHFR
- Uniprot ID
- P00374
- Uniprot Name
- Dihydrofolate reductase
- Molecular Weight
- 21452.61 Da
References
- 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
- 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...
- Gene Name
- AOX1
- Uniprot ID
- Q06278
- Uniprot Name
- Aldehyde oxidase
- Molecular Weight
- 147916.735 Da
References
- 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]
- 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]
- 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
- Uniprot Name
- Methylenetetrahydrofolate reductase
- Molecular Weight
- 74595.895 Da
References
- Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865]
- 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
- Uniprot Name
- 6-phosphogluconate dehydrogenase, decarboxylating
- Molecular Weight
- 53139.56 Da
References
- 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]
- 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 substrate...
- Gene Name
- FPGS
- Uniprot ID
- Q05932
- Uniprot Name
- Folylpolyglutamate synthase, mitochondrial
- Molecular Weight
- 64608.53 Da
References
- 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
- Uniprot Name
- Thymidylate synthase
- Molecular Weight
- 35715.65 Da
References
- 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
- Uniprot Name
- Bifunctional purine biosynthesis protein PURH
- Molecular Weight
- 64615.255 Da
References
- 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 fr...
- Gene Name
- GGH
- Uniprot ID
- Q92820
- Uniprot Name
- Gamma-glutamyl hydrolase
- Molecular Weight
- 35964.045 Da
References
- 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
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Vecht CJ, Wagner GL, Wilms EB: Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol. 2003 Jul;2(7):404-9. [PubMed:12849118]
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 colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- 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]
- 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 hepatocyte...
- Gene Name
- ABCC3
- Uniprot ID
- O15438
- Uniprot Name
- Canalicular multispecific organic anion transporter 2
- Molecular Weight
- 169341.14 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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
- Uniprot Name
- Multidrug resistance-associated protein 4
- Molecular Weight
- 149525.33 Da
References
- 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]
- 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]
- 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]
- 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, methotre...
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- 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]
- 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]
- 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 ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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
- Uniprot Name
- Multidrug resistance-associated protein 7
- Molecular Weight
- 161627.375 Da
References
- 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, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
References
- 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]
- 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]
- 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]
- 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]
- 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
- Uniprot Name
- Canalicular multispecific organic anion transporter 1
- Molecular Weight
- 174205.64 Da
References
- 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]
- 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]
- 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]
- 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]
- 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
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- 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 inhibit...
- Gene Name
- SLCO1A2
- Uniprot ID
- P46721
- Uniprot Name
- Solute carrier organic anion transporter family member 1A2
- Molecular Weight
- 74144.105 Da
References
- 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 leucin...
- Gene Name
- SLC16A1
- Uniprot ID
- P53985
- Uniprot Name
- Monocarboxylate transporter 1
- Molecular Weight
- 53943.685 Da
References
- 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 ...
- Gene Name
- ABCC11
- Uniprot ID
- Q96J66
- Uniprot Name
- ATP-binding cassette sub-family C member 11
- Molecular Weight
- 154299.625 Da
References
- 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), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- 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
- Uniprot Name
- Solute carrier family 22 member 11
- Molecular Weight
- 59970.945 Da
References
- 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-gluc...
- Gene Name
- SLCO1C1
- Uniprot ID
- Q9NYB5
- Uniprot Name
- Solute carrier organic anion transporter family member 1C1
- Molecular Weight
- 78695.625 Da
References
- 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 an...
- Gene Name
- SLCO3A1
- Uniprot ID
- Q9UIG8
- Uniprot Name
- Solute carrier organic anion transporter family member 3A1
- Molecular Weight
- 76552.135 Da
References
- 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 fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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 sulf...
- Gene Name
- SLC22A7
- Uniprot ID
- Q9Y694
- Uniprot Name
- Solute carrier family 22 member 7
- Molecular Weight
- 60025.025 Da
References
- 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]
- 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
- 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 epithel...
- Gene Name
- SLC46A1
- Uniprot ID
- Q96NT5
- Uniprot Name
- Proton-coupled folate transporter
- Molecular Weight
- 49770.04 Da
References
- 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
- 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, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- 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]
- 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
- 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 ...
- Gene Name
- SLCO4C1
- Uniprot ID
- Q6ZQN7
- Uniprot Name
- Solute carrier organic anion transporter family member 4C1
- Molecular Weight
- 78947.525 Da
References
- 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 th...
- Gene Name
- SLC19A1
- Uniprot ID
- P41440
- Uniprot Name
- Folate transporter 1
- Molecular Weight
- 64867.62 Da
References
- 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 analo...
- Gene Name
- FOLR1
- Uniprot ID
- P15328
- Uniprot Name
- Folate receptor alpha
- Molecular Weight
- 29818.94 Da
References
- 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]
Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:43