Identification

Name
Methotrexate
Accession Number
DB00563
Description

Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis.1 This inhibition leads to suppression of inflammation as well as prevention of cell division.1 Because of these effects, methotrexate is often used to treat inflammation caused by arthritis or to control cell division in neoplastic diseases such as breast cancer and non-Hodgkin's lymphoma.1,4,5,6,7

Due to the toxic effects of methotrexate, it is indicated for treatment of some forms of arthritis and severe psoriasis only if first line treatment has failed or patients are intolerant of those treatments.7

Methotrexate was granted FDA approval on 7 December 1953.8

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 454.4393
Monoisotopic: 454.171315854
Chemical Formula
C20H22N8O5
Synonyms
  • 4-amino-10-methylfolic acid
  • 4-amino-N(10)-methylpteroylglutamic acid
  • Amethopterin
  • Methotrexat
  • Méthotrexate
  • Methotrexate
  • 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

Pharmacology

Indication

Methotrexate oral solution is indicated for pediatric acute lymphoblastic leukemia and pediatric polyarticular juvenile idiopathic arthritis.4 Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis.5,6,10

Other formulations are indicated to treat gestational choriocarcinoma, chorioadenoma destruens, hydatiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin's lymphoma.7 It is also used in the maintenance of acute lymphocytic leukemia.7 Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma.7

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions.1 It has a long duration of action and is generally given to patients once weekly.1,4,5,6 Methotrexate has a narrow therapeutic index.2

Do not take methotrexate daily.5,6

Mechanism of action

Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate.1

Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase.1 Inhibtion of nucleotide synthesis prevents cell division.

In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate.1 This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.1

TargetActionsOrganism
ADihydrofolate reductase
inhibitor
Humans
AThymidylate synthase
inhibitor
Humans
ABifunctional purine biosynthesis protein PURH
inhibitor
Humans
Absorption

Methotrexate has a bioavailability of 64-90%, though this decreases at oral doses above 25mg due to saturation of the carrier mediated transport of methotrexate.1. Methotrexate has a Tmax of 1 to 2 hours.1 oral doses of 10-15µg reach serum levels of 0.01-0.1µM.1

Volume of distribution

The volume of distribution of methotrexate at steady state is approximately 1L/kg.1

Protein binding

Methotrexate is 46.5-54% bound to plasma proteins.1

Metabolism

Methotrexate is metabolized by folylpolyglutamate synthase to methotrexate polyglutamate in the liver as well as in tissues.1,7 Gamma-glutamyl hydrolase hydrolyzes the glutamyl chains of methotrexate polyglutamates converting them back to methotrexate.1,7 A small amount of methotrexate is also converted to 7-hydroxymethotrexate.1,7

Hover over products below to view reaction partners

Route of elimination

Methotrexate is >80% excreted as the unchanged drug and approximately 3% as the 7-hydroxylated metabolite.1 Methotrexate is primarily excreted in the urine with 8.7-26% of an intravenous dose appearing in the bile.1

Half-life

The half life of low dose methotrexate is 3 to 10 hours in adults.4 The half life for high dose methotrexate is 8 to 15 hours.5 Pediatric patients taking methotrexate for acute lymphoblastic anemia experience a terminal half life of 0.7 to 5.8 hours.4 Pediatric patients taking methotrexate for juvenile idiopathic arthritis experience a half life of 0.9 to 2.3 hours.4

Clearance

Methotrexate clearance varies widely between patients and decreases with increasing doses.3 Currently, predicting clearance of methotrexate is difficult and exceedingly high serum levels of methotrexate can still occur when all precautions are taken.3

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The oral LD50 in rats is 135mg/kg and in mice is 146mg/kg.9

Symptoms of overdose include hematologic and gastrointestinal reactions like leukopenia, thombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, and gastrointestinal bleeding.7 In the event of an overdose, patients should be treated with glucarpidase and not be given leucovorin for 2 hours before or after glucarpidase.7

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Methotrexate Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Canalicular multispecific organic anion transporter 1ABCC2 IVS 23+56(C;C) / (C;T)T alleleADR Directly StudiedPatients with this genotype have increased risk of toxicity with methotrexate.Details
Methylenetetrahydrofolate reductase---(T;T) / (C;T)T alleleADR Directly StudiedPatients with this genotype have increased risk of toxicity with methotrexate.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMethotrexate may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe metabolism of Methotrexate can be decreased when combined with Abametapir.
AbataceptThe metabolism of Abatacept can be increased when combined with Methotrexate.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Methotrexate.
AbemaciclibAbemaciclib may decrease the excretion rate of Methotrexate which could result in a higher serum level.
AcalabrutinibThe metabolism of Methotrexate can be decreased when combined with Acalabrutinib.
AcarboseMethotrexate may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacThe serum concentration of Methotrexate can be increased when it is combined with Aceclofenac.
AcemetacinThe serum concentration of Methotrexate can be increased when it is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Methotrexate.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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  • Action
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Food Interactions
  • Avoid alcohol.
  • Avoid milk and dairy products. Milk and dairy products reduce absorption.
  • Exercise caution with St. John's Wort.
  • Limit caffeine intake. Caffeine may reduce the effectiveness of methotrexate.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Methotrexate sodium3IG1E710ZN7413-34-5DASQOOZCTWOQPA-UHFFFAOYSA-L
Product Images
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)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MethotrexateInjection, solution25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousHospira, Inc.2001-02-26Not applicableUS flag
MethotrexateInjection, solution25 mg/1mLIntra-arterial; Intramuscular; IntravenousHospira, Inc.2008-02-252008-02-25US flag
MethotrexateInjection, solution17.5 mg/0.7mLSubcutaneousAntares Pharma, Inc.2017-12-012017-12-01US flag
MethotrexateTablet2.5 mg/1OralRemedy Repack2016-03-112017-01-24US flag
MethotrexateTablet2.5 mg/1OralDispensing Solutions, Inc.1953-12-07Not applicableUS flag67253 0320 10 nlmimage10 f008f857
MethotrexateSolution25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousThyMoorgan GmbH Pharmazir & Co. K.G2018-01-05Not applicableUS flag
MethotrexateInjection, solution22.5 mg/0.9mLSubcutaneousAntares Pharma, Inc.2017-12-012017-12-01US flag
MethotrexateInjection, solution25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousHospira Worldwide, Inc.2012-03-022014-01-31US flag
MethotrexateInjection, solution15 mg/0.6mLSubcutaneousAntares Pharma, Inc.2017-12-012017-12-01US flag
MethotrexateTablet2.5 mg/1OralPar Pharmaceutical, Inc.1953-12-072021-02-28US flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-methotrexateTabletOralApotex Corporation1999-09-17Not applicableCanada flag
Jamp-methotrexateSolutionIntra-arterial; Intramuscular; Intrathecal; IntravenousJamp Pharma Corporation2014-03-12Not applicableCanada flag
MethotrexateInjection, solution25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousTeva Parenteral Medicines, Inc.2012-08-012014-04-30US flag
MethotrexateSolution25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousHikma Pharmaceuticals USA Inc.2018-01-05Not applicableUS flag
MethotrexateInjection, powder, lyophilized, for solution1 g/1Intra-arterial; Intramuscular; Intrathecal; IntravenousHikma Pharmaceuticals USA Inc.2005-09-06Not applicableUS flag
MethotrexateTablet2.5 mg/1OralGolden State Medical Supply1992-05-18Not applicableUS flag
MethotrexateInjection, solution25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousBedford Pharmaceuticals1996-05-012012-10-31US flag
MethotrexateInjection, solution25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousFresenius Kabi USA, LLC2003-04-032015-11-23US flag
MethotrexateTablet2.5 mg/1OralMylan Institutional Inc.1995-07-13Not applicableUS flag00378 0014 01 nlmimage10 b944dc96
MethotrexateInjection25 mg/1mLIntra-arterial; Intramuscular; Intrathecal; IntravenousPfizer Laboratories Div Pfizer Inc.2012-03-302017-12-31US flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
MethotrexateMethotrexate sodium (25 mg/1mL)Injection, solutionIntra-arterial; Intramuscular; Intrathecal; IntravenousHospira Worldwide, Inc.2012-03-022014-01-31US flag

Categories

ATC Codes
L04AX03 — MethotrexateL01BA01 — Methotrexate
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Amine / Amino acid / Aminobenzamide / Aminobenzoic acid or derivatives / Aminopyrimidine / Aniline or substituted anilines / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzamide
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid amide, dicarboxylic acid, pteridines (CHEBI:44185)

Chemical Identifiers

UNII
YL5FZ2Y5U1
CAS number
59-05-2
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-{[(4-amino-2-imino-2,3-dihydropteridin-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[[email protected]@H](CCC(O)=O)C(O)=O

References

Synthesis Reference
US2512572
General References
  1. Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26. [PubMed:24284432]
  2. Przekop PR Jr, Tulgan H, Przekop AA, Glantz M: Adverse drug reaction to methotrexate: pharmacogenetic origin. J Am Osteopath Assoc. 2006 Dec;106(12):706-7. [PubMed:17242415]
  3. Muhrez K, Benz-de Bretagne I, Nadal-Desbarats L, Blasco H, Gyan E, Choquet S, Montigny F, Emond P, Barin-Le Guellec C: Endogenous metabolites that are substrates of organic anion transporter's (OATs) predict methotrexate clearance. Pharmacol Res. 2017 Apr;118:121-132. doi: 10.1016/j.phrs.2016.05.021. Epub 2016 May 19. [PubMed:27210722]
  4. FDA Approved Drug Products: Methotrexate Oral Solution [Link]
  5. FDA Approved Drug Products: Methotrexate Subcutaneous Injection [Link]
  6. FDA Approved Drug Products: Methotrexate Prefilled Syringe for Subcutaneous Injection [Link]
  7. FDA Approved Drug Products: Methotrexate Injection [Link]
  8. FDA Approved Drug Products: Methotrexate Sodium Oral Tablets [Link]
  9. Cayman Chemicals: Methotrexate MSDS [Link]
  10. FDA Approved Drug Products: RediTrex Methotrexate Subcutaneous Injection [Link]
Human Metabolome Database
HMDB0014703
KEGG Drug
D00142
KEGG Compound
C01937
PubChem Compound
126941
PubChem Substance
46507678
ChemSpider
112728
BindingDB
66082
RxNav
6851
ChEBI
44185
ChEMBL
CHEMBL34259
ZINC
ZINC000001529323
Therapeutic Targets Database
DNC000933
PharmGKB
PA450428
PDBe Ligand
MTX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Methotrexate
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
1ao8 / 1axw / 1d1g / 1ddr / 1dds / 1df7 / 1dhi / 1dhj / 1dls / 1dra
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FDA label
Download (518 KB)
MSDS
Download (77 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentCrohn's Disease (CD)2
4Active Not RecruitingTreatmentGouty Arthritis2
4Active Not RecruitingTreatmentRheumatoid Arthritis2
4Active Not RecruitingTreatmentUlcerative Colitis1
4CompletedNot AvailableRelapsing Remitting Multiple Sclerosis (RRMS)1
4CompletedNot AvailableRheumatoid Arthritis1
4CompletedBasic SciencePsoriasis1
4CompletedBasic ScienceRheumatoid Arthritis2
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)5
4CompletedTreatmentAdult Acute Lymphocytic Leukemia4

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
FormRouteStrength
InjectionSubcutaneous10 mg/mL
InjectionSubcutaneous20 mg/2.0mL
Injection, solutionSubcutaneous7.5 mg/0.75ml
Injection, solutionParenteral50 MG
InjectionIntravenous1 g/10ml
InjectionIntravenous500 mg/20ml
InjectionIntravenous50 mg/2ml
SolutionParenteral10 mg/ml
Injection, solutionParenteral10 mg/ml
Injection, solution, concentrateParenteral100 mg/ml
Injection, solutionParenteral20 mg/ml
Injection, solutionIntramuscular; Intrathecal; Intravenous1000 MG
Injection, solutionIntramuscular; Intrathecal; Intravenous50 MG
TabletOral2.5 MG
Injection10 mg/0.4ml
Injection15 mg/0.6ml
Injection20 mg/0.8ml
Injection25 mg/ml
InjectionIntramuscular; Intravenous15 mg/3ml
TabletOral10 MG
TabletOral7.5 MG
Injection, solutionParenteral10 MG
Injection, solutionParenteral15 MG
Injection, solutionParenteral
Injection, solutionParenteral25 MG
Injection, solutionParenteral7.5 MG
Injection, solutionParenteral12.5 MG
Injection, solutionParenteral17.5 MG
Injection, solutionParenteral20 MG
Injection, solutionParenteral22.5 MG
Injection, solutionParenteral27.5 MG
Injection, solutionParenteral30 MG
Injection, solutionSubcutaneous10 mg/1ml
Injection, solutionSubcutaneous15 mg/1.5ml
Injection, solutionSubcutaneous20 mg/2ml
InjectionParenteral25 mg
Injection, solutionParenteral1000 MG/40ML
Injection, solutionParenteral500 MG/20ML
Injection, solutionParenteral50 MG/2ML
Injection, solution, concentrateIntravenous100 mg/ml
SolutionParenteral1 G/10ML
SolutionParenteral5 G/50ML
Injection, solutionParenteral10 MG/0.4ML
Injection, solutionParenteral15 MG/0.6ML
Injection, solutionParenteral20 MG/0.8ML
Injection, solutionParenteral25 MG/1.0ML
Injection, solutionParenteral7.5 MG/0.3ML
Injection, solution, concentrateIntramuscular; Intravenous50 mg/5ml
Injection, solution, concentrateIntramuscular; Intravenous500 mg/5ml
Injection, solutionIntramuscular; Intravenous; Intravenous bolus; Subcutaneous7.5 mg/0.75ml
Injection, solutionParenteral2.5 mg/ml
InjectionParenteral25 mg/ml
InjectionParenteral50 mg/2ml
Injection, solutionParenteral1000 MG
Injection, solutionParenteral5000 MG
Injection, solution50 mg/5mL
Injection, solution500 mg/5mL
SolutionParenteral1000 mg/10ml
Injection, solutionParenteral5 mg/2ml
SolutionParenteral500 mg/20ml
SolutionParenteral5000 mg/50ml
Injection
InjectionIntra-arterial; Intramuscular; Intrathecal; Intravenous25 mg/1mL
Injection, powder, for solution1 G
Injection, powder, for solution5 MG
Injection, powder, for solution50 MG
Injection, powder, for solution500 MG
Injection, powder, lyophilized, for solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous1 g/1
Injection, powder, lyophilized, for solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous1 g/20mL
Injection, solution500 mg/20mg
Injection, solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous1 g/40mL
Injection, solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous25 mg/1mL
Injection, solutionIntra-arterial; Intramuscular; Intravenous10 mg/1mL
Injection, solutionIntra-arterial; Intramuscular; Intravenous25 mg/1mL
Injection, solutionParenteral1 G/10ML
Injection, solutionParenteral10 MG/1.33ML
Injection, solutionParenteral15 MG/2ML
Injection, solutionParenteral20 MG/2.66ML
Injection, solutionParenteral5 G/50ML
Injection, solutionSubcutaneous10 mg/0.4mL
Injection, solutionSubcutaneous15 mg/0.6mL
Injection, solutionSubcutaneous17.5 mg/0.7mL
Injection, solutionSubcutaneous20 mg/0.8mL
Injection, solutionSubcutaneous22.5 mg/0.9mL
Injection, solutionSubcutaneous25 mg/1mL
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous25 mg/1mL
SolutionIntra-arterial; Intramuscular; Intravenous25 mg
Tablet, coatedOral2.5 mg
Injection, solution, concentrateIntra-arterial; Intramuscular; Intrathecal; Intravenous50 mg/5ml
Injection, solutionIntra-arterial; Intramuscular; Intravenous50 mg/2ml
Injection, solutionIntramuscular; Intravenous500 mg/20ml
Injection, solutionIntramuscular; Intravenous5 gr/50ml
LiquidIntravenous
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous
SolutionIntravenous
Injection500 mg/20ml
Injection, solutionIntra-arterial; Intramuscular; Intrathecal; Iontophoresis25 mg/1mL
TabletOral2.5 mg/1
Powder, for solutionIntramuscular; Intrathecal; Intravenous
LiquidIntramuscular; Intrathecal; Intravenous
LiquidIntra-arterial; Intramuscular; Intrathecal; Intravenous
SolutionIntra-arterial; Intramuscular; Intrathecal; Intravenous; Intraventricular
Powder, for solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous
InjectionSubcutaneous10 mg/1ml
InjectionSubcutaneous15 mg/1.5ml
InjectionSubcutaneous20 mg/2ml
InjectionSubcutaneous25 mg/2.5ml
Injection10 mg/0.25ml
Injection12.5 mg/0.3125ml
Injection15 mg/0.375ml
Injection17.5 mg/0.4375ml
Injection20 mg/0500ml
Injection22.5 mg/0.5625ml
Injection25 mg/0.625ml
Injection27.5 mg/0.6875ml
Injection30 mg/0.75ml
Injection7.5 mg/0.1875ml
SolutionIntra-arterial; Intramuscular; Intravenous
Injection, solutionIntramuscular; Intravenous; Subcutaneous10 mg/1ml
Injection, solutionIntramuscular; Intravenous; Subcutaneous15 mg/1.5ml
Injection, solutionIntramuscular; Intravenous; Subcutaneous20 mg/2ml
Injection, solutionIntramuscular; Intravenous; Subcutaneous25 mg/2.5ml
SolutionSubcutaneous
SolutionSubcutaneous10 mg
SolutionSubcutaneous15 mg
SolutionSubcutaneous20 mg
SolutionSubcutaneous25 mg
SolutionIntravenous; Subcutaneous7.5 mg
Injection, solutionParenteral50 MG/ML
Injection, solutionParenteral100 MG/ML
Injection, solutionParenteral25 MG/ML
Injection, powder, lyophilized, for solutionIntravenous50 mg
Injection, powder, lyophilized, for solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous500 mg
Injection, solutionIntra-arterial; Intramuscular; Intrathecal; Intravenous25 MG/ML
Injection, solution, concentrateIntra-arterial; Intramuscular; Intravenous100 MG/ML
Injection, solutionParenteral2.5 MG
Injection, solution1 G/10ML
Injection, solution1 G/40ML
Injection, solution100 MG/4ML
Injection, solution5 G/50ML
Injection, solution5 MG/2ML
Injection, solution50 MG/2ML
Injection, solution500 MG/20ML
Injection, powder, lyophilized, for solutionIntramuscular; Intrathecal; Intravenous500 mg
InjectionIntramuscular; Intravenous1000 mg/40ml
InjectionIntramuscular; Intravenous50 mg/2ml
InjectionIntramuscular; Intravenous5000 mg/50ml
InjectionIntramuscular; Intravenous500 mg/20ml
Injection, solutionParenteral10 mg/4ml
TabletOral15 MG
TabletOral5 MG
Injection, solutionParenteral7.5 MG/ML
SolutionIntramuscular; Intrathecal; Intravenous; Subcutaneous25 mg
Injection, solutionCutaneous10 MG
Injection, solutionCutaneous12.5 MG
Injection, solutionCutaneous15 MG
Injection, solutionCutaneous17.5 MG
Injection, solutionCutaneous20 MG
Injection, solutionCutaneous22.5 MG
Injection, solutionCutaneous25 MG
Injection, solutionCutaneous7.5 MG
Injection, solutionSubcutaneous10 mg
Injection, solutionSubcutaneous12.5 mg
Injection, solutionSubcutaneous15 mg
Injection, solutionSubcutaneous17.5 mg
Injection, solutionSubcutaneous20 mg
Injection, solutionSubcutaneous22.5 mg
Injection, solutionSubcutaneous25 mg
Injection, solutionSubcutaneous7.5 mg
Injection, solutionSubcutaneous12.5 mg/0.4mL
Injection, solutionSubcutaneous15 mg/0.4mL
Injection, solutionSubcutaneous17.5 mg/0.4mL
Injection, solutionSubcutaneous20 mg/0.4mL
Injection, solutionSubcutaneous22.5 mg/0.4mL
Injection, solutionSubcutaneous25 mg/0.4mL
Injection, solutionSubcutaneous7.5 mg/0.4mL
Injection, solutionSubcutaneous10 mg/0.2mL
Injection, solutionSubcutaneous12.5 mg/0.25mL
Injection, solutionSubcutaneous15 mg/0.3mL
Injection, solutionSubcutaneous17.5 mg/0.35mL
Injection, solutionSubcutaneous22.5 mg/0.45mL
Injection, solutionSubcutaneous25 mg/0.5mL
Injection, solutionSubcutaneous27.5 mg/0.55mL
Injection, solutionSubcutaneous30 mg/0.6mL
Injection, solutionSubcutaneous7.5 mg/0.15mL
TabletOral
Injection, solutionSubcutaneous12.5 mg/0.5mL
Injection, solutionSubcutaneous7.5 mg/0.3mL
Injection, solutionCutaneous; Parenteral50 MG/ML
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral15 mg/1
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral7.5 mg/1
SolutionOral2.5 mg/1mL
Injection, solution15 mg/3ml
Injection, solutionIntravenous500 mg/20ml
Prices
Unit descriptionCostUnit
Methotrexate powder261.33USD g
Rheumatrex 8 2.5 mg tablet Disp Pack169.98USD disp
Rheumatrex 24 2.5 mg tablet Disp Pack129.06USD disp
Rheumatrex 20 2.5 mg tablet Disp Pack107.59USD disp
Rheumatrex 12 2.5 mg tablet Disp Pack63.65USD disp
Methotrexate Sodium 25 mg/ml (pf) Solution 40ml Vial58.99USD vial
Trexall 15 mg tablet25.98USD tablet
Methotrexate Sodium 25 mg/ml (pf) Solution 10ml Vial24.99USD vial
Trexall 10 mg tablet17.67USD tablet
Methotrexate Sodium 25 mg/ml Solution 1 Vial = 2ml15.11USD vial
Methotrexate Sodium 25 mg/ml (pf) Solution 2ml Vial14.99USD vial
Trexall 7.5 mg tablet12.99USD tablet
Rheumatrex 2.5 mg tablet11.23USD tablet
Trexall 5 mg tablet8.66USD tablet
Methotrexate Sod. (Preserved) 25 mg/ml8.38USD ml
Methotrexate Sod.(Unpreserved) 25 mg/ml4.56USD ml
Methotrexate 2.5 mg tablet2.71USD tablet
Methotrexate 10 mg Tablet2.58USD tablet
Ratio-Methotrexate Sodium 2.5 mg Tablet0.66USD tablet
Apo-Methotrexate 2.5 mg Tablet0.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8480631No2013-07-092030-03-19US flag
USRE44847No2014-04-152019-08-10US flag
US8579865No2013-11-122030-03-19US flag
US8945063No2015-02-032030-03-19US flag
USRE44846No2014-04-152019-08-10US flag
US8021335No2011-09-202026-10-04US flag
US6746429No2004-06-082020-04-12US flag
US8562564No2013-10-222026-01-24US flag
US7744582No2010-06-292019-08-10US flag
US7776015No2010-08-172019-08-10US flag
US8664231No2014-03-042029-06-01US flag
US9533102No2017-01-032026-01-24US flag
US9629959No2017-04-252026-01-24US flag
US9421333No2016-08-232030-03-19US flag
US9259427No2016-02-162033-01-02US flag
US9855215No2018-01-022033-01-02US flag
US10231927No2019-03-192033-01-02US flag
US10610485No2013-01-022033-01-02US flag
US8814834No2011-05-272031-05-27US flag
US9867949No2009-03-102029-03-10US flag
US10709844No2009-03-102029-03-10US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)195 °Chttp://www.chemspider.com/Chemical-Structure.112728.html?rid=5b5d388b-5afb-4024-803b-99539fa66a77
logP-1.85HANSCH,C ET AL. (1995)
Caco2 permeability-5.92ADME Research, USCD
pKa4.7SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0819 mg/mLALOGPS
logP-0.05ALOGPS
logP-2.3ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)2.95ChemAxon
pKa (Strongest Basic)14.55ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area205.92 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity137.57 m3·mol-1ChemAxon
Polarizability45.43 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.8261
Blood Brain Barrier-0.9467
Caco-2 permeable-0.7754
P-glycoprotein substrateSubstrate0.8172
P-glycoprotein inhibitor INon-inhibitor0.7752
P-glycoprotein inhibitor IINon-inhibitor0.9879
Renal organic cation transporterNon-inhibitor0.8886
CYP450 2C9 substrateNon-substrate0.85
CYP450 2D6 substrateNon-substrate0.7968
CYP450 3A4 substrateSubstrate0.5177
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8333
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9739
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9517
BiodegradationNot ready biodegradable0.9741
Rat acute toxicity3.4955 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9564
hERG inhibition (predictor II)Non-inhibitor0.6958
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10.1 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0fai-6900000000-25b0e287457fb3845ef4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-1819500000-3159955c0d961d305b13
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0619400000-9a6d686008b68ac436ba
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-2902000000-526ede2e4de609cb3d44
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Targets

Details
1. Dihydrofolate reductase
Kind
Protein
Organism
Humans
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
  1. Al-Rashood ST, Aboldahab IA, Nagi MN, Abouzeid LA, Abdel-Aziz AA, Abdel-Hamide SG, Youssef KM, Al-Obaid AM, El-Subbagh HI: Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs. Bioorg Med Chem. 2006 Dec 15;14(24):8608-21. Epub 2006 Sep 12. [PubMed:16971132]
  2. Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007 Mar;26(1):153-81. [PubMed:17333344]
  3. Bennett B, Langan P, Coates L, Mustyakimov M, Schoenborn B, Howell EE, Dealwis C: Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18493-8. Epub 2006 Nov 27. [PubMed:17130456]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. Totani K, Matsuo I, Ihara Y, Ito Y: High-mannose-type glycan modifications of dihydrofolate reductase using glycan-methotrexate conjugates. Bioorg Med Chem. 2006 Aug 1;14(15):5220-9. Epub 2006 May 2. [PubMed:16647263]
  6. Uga H, Kuramori C, Ohta A, Tsuboi Y, Tanaka H, Hatakeyama M, Yamaguchi Y, Takahashi T, Kizaki M, Handa H: A new mechanism of methotrexate action revealed by target screening with affinity beads. Mol Pharmacol. 2006 Nov;70(5):1832-9. Epub 2006 Aug 25. [PubMed:16936229]
  7. Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26. [PubMed:24284432]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
  1. Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26. [PubMed:24284432]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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
  1. Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26. [PubMed:24284432]

Enzymes

Kind
Protein
Organism
Humans
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
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865]
Kind
Protein
Organism
Humans
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
  1. Zientek M, Jiang Y, Youdim K, Obach RS: In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase. Drug Metab Dispos. 2010 Aug;38(8):1322-7. doi: 10.1124/dmd.110.033555. Epub 2010 May 5. [PubMed:20444863]
  2. Baggott JE, Morgan SL: Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. Arthritis Rheum. 2009 Aug;60(8):2257-61. doi: 10.1002/art.24685. [PubMed:19644884]
  3. Jordan CG, Rashidi MR, Laljee H, Clarke SE, Brown JE, Beedham C: Aldehyde oxidase-catalysed oxidation of methotrexate in the liver of guinea-pig, rabbit and man. J Pharm Pharmacol. 1999 Apr;51(4):411-8. [PubMed:10385213]
Kind
Protein
Organism
Humans
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
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865]
  2. Kremer JM: Methotrexate pharmacogenomics. Ann Rheum Dis. 2006 Sep;65(9):1121-3. [PubMed:16905578]
Kind
Protein
Organism
Humans
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
  1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. doi: 10.3109/14756360903257900. [PubMed:20235752]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Humans
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
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865]
Details
6. Thymidylate synthase
Kind
Protein
Organism
Humans
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
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865]
Kind
Protein
Organism
Humans
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
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865]
Kind
Protein
Organism
Humans
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
  1. Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. Epub 2007 Jun 24. [PubMed:17586865]
Kind
Protein
Organism
Humans
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
  1. 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
Humans
Pharmacological action
No
Actions
Binder
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
  1. Warnecke A, Fichtner I, Sass G, Kratz F: Synthesis, cleavage profile, and antitumor efficacy of an albumin-binding prodrug of methotrexate that is cleaved by plasmin and cathepsin B. Arch Pharm (Weinheim). 2007 Aug;340(8):389-95. [PubMed:17628030]
  2. Xie WJ, Feng YP, Cao SL, Zhao YF: [Study of the interaction between methotrexate and bovine serum albumin by spectrometry]. Guang Pu Xue Yu Guang Pu Fen Xi. 2006 Oct;26(10):1876-9. [PubMed:17205742]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Akita H, Suzuki H, Hirohashi T, Takikawa H, Sugiyama Y: Transport activity of human MRP3 expressed in Sf9 cells: comparative studies with rat MRP3. Pharm Res. 2002 Jan;19(1):34-41. [PubMed:11837698]
  2. Oleschuk CJ, Deeley RG, Cole SP: Substitution of Trp1242 of TM17 alters substrate specificity of human multidrug resistance protein 3. Am J Physiol Gastrointest Liver Physiol. 2003 Feb;284(2):G280-9. Epub 2002 Oct 9. [PubMed:12388190]
  3. Hirohashi T, Suzuki H, Sugiyama Y: Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3). J Biol Chem. 1999 May 21;274(21):15181-5. [PubMed:10329726]
  4. Zeng H, Liu G, Rea PA, Kruh GD: Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res. 2000 Sep 1;60(17):4779-84. [PubMed:10987286]
  5. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759]
  6. Paumi CM, Wright M, Townsend AJ, Morrow CS: Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-Delta(12,14)prostaglandin J2 in MCF7 breast cancer cells. Biochemistry. 2003 May 13;42(18):5429-37. [PubMed:12731885]
  7. Li T, Ito K, Horie T: Transport of fluorescein methotrexate by multidrug resistance-associated protein 3 in IEC-6 cells. Am J Physiol Gastrointest Liver Physiol. 2003 Sep;285(3):G602-10. [PubMed:12909565]
  8. Zehnpfennig B, Urbatsch IL, Galla HJ: Functional reconstitution of human ABCC3 into proteoliposomes reveals a transport mechanism with positive cooperativity. Biochemistry. 2009 May 26;48(20):4423-30. doi: 10.1021/bi9001908. [PubMed:19334674]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Chen ZS, Lee K, Kruh GD: Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J Biol Chem. 2001 Sep 7;276(36):33747-54. Epub 2001 Jul 10. [PubMed:11447229]
  2. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. [PubMed:12883481]
  3. Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [PubMed:14643890]
  4. van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG: The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol. 2002 Mar;13(3):595-603. [PubMed:11856762]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J: Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta. 1997 May 22;1326(1):12-22. [PubMed:9188796]
  2. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759]
  3. Paumi CM, Wright M, Townsend AJ, Morrow CS: Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-Delta(12,14)prostaglandin J2 in MCF7 breast cancer cells. Biochemistry. 2003 May 13;42(18):5429-37. [PubMed:12731885]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Lu R, Chan BS, Schuster VL: Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2 Pt 2):F295-303. [PubMed:9950961]
  2. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [PubMed:9880528]
  3. Uwai Y, Okuda M, Takami K, Hashimoto Y, Inui K: Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Lett. 1998 Nov 6;438(3):321-4. [PubMed:9827570]
  4. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730]
  5. Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H: Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem. 1997 Jul 25;272(30):18526-9. [PubMed:9228014]
  6. Uwai Y, Iwamoto K: Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9. [PubMed:20460822]
Kind
Protein
Organism
Humans
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
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [PubMed:12527806]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [PubMed:14762099]
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140]
  3. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [PubMed:11306713]
  4. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730]
  5. Uwai Y, Iwamoto K: Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9. [PubMed:20460822]
  6. VanWert AL, Sweet DH: Impaired clearance of methotrexate in organic anion transporter 3 (Slc22a8) knockout mice: a gender specific impact of reduced folates. Pharm Res. 2008 Feb;25(2):453-62. doi: 10.1007/s11095-007-9407-0. Epub 2007 Jul 28. [PubMed:17660957]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Han YH, Kato Y, Haramura M, Ohta M, Matsuoka H, Sugiyama Y: Physicochemical parameters responsible for the affinity of methotrexate analogs for rat canalicular multispecific organic anion transporter (cMOAT/MRP2). Pharm Res. 2001 May;18(5):579-86. [PubMed:11465411]
  2. Masuda M, I'izuka Y, Yamazaki M, Nishigaki R, Kato Y, Ni'inuma K, Suzuki H, Sugiyama Y: Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats. Cancer Res. 1997 Aug 15;57(16):3506-10. [PubMed:9270020]
  3. Hooijberg JH, Broxterman HJ, Kool M, Assaraf YG, Peters GJ, Noordhuis P, Scheper RJ, Borst P, Pinedo HM, Jansen G: Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res. 1999 Jun 1;59(11):2532-5. [PubMed:10363967]
  4. Bakos E, Evers R, Sinko E, Varadi A, Borst P, Sarkadi B: Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol. 2000 Apr;57(4):760-8. [PubMed:10727523]
  5. Chen C, Scott D, Hanson E, Franco J, Berryman E, Volberg M, Liu X: Impact of Mrp2 on the biliary excretion and intestinal absorption of furosemide, probenecid, and methotrexate using Eisai hyperbilirubinemic rats. Pharm Res. 2003 Jan;20(1):31-7. [PubMed:12608533]
Kind
Protein
Organism
Humans
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
  1. Norris MD, De Graaf D, Haber M, Kavallaris M, Madafiglio J, Gilbert J, Kwan E, Stewart BW, Mechetner EB, Gudkov AV, Roninson IB: Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate. Int J Cancer. 1996 Mar 1;65(5):613-9. [PubMed:8598312]
Kind
Protein
Organism
Humans
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
  1. Cattori V, van Montfoort JE, Stieger B, Landmann L, Meijer DK, Winterhalter KH, Meier PJ, Hagenbuch B: Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95. [PubMed:11713643]
Kind
Protein
Organism
Humans
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
  1. Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S, Tsuji A: Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol. 1999 Oct;51(10):1113-21. [PubMed:10579682]
Kind
Protein
Organism
Humans
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
  1. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. [PubMed:15537867]
Kind
Protein
Organism
Humans
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
  1. Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R, Adachi H, Fujiwara K, Okabe M, Suzuki T, Nunoki K, Sato E, Kakyo M, Nishio T, Sugita J, Asano N, Tanemoto M, Seki M, Date F, Ono K, Kondo Y, Shiiba K, Suzuki M, Ohtani H, Shimosegawa T, Iinuma K, Nagura H, Ito S, Matsuno S: LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99. [PubMed:11375950]
Kind
Protein
Organism
Humans
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
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730]
Kind
Protein
Organism
Humans
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
  1. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [PubMed:12351693]
Kind
Protein
Organism
Humans
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
  1. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. [PubMed:14631946]
Kind
Protein
Organism
Humans
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
  1. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y: ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7. [PubMed:12682043]
  2. Breedveld P, Zelcer N, Pluim D, Sonmezer O, Tibben MM, Beijnen JH, Schinkel AH, van Tellingen O, Borst P, Schellens JH: Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004 Aug 15;64(16):5804-11. [PubMed:15313923]
  3. Mitomo H, Kato R, Ito A, Kasamatsu S, Ikegami Y, Kii I, Kudo A, Kobatake E, Sumino Y, Ishikawa T: A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport. Biochem J. 2003 Aug 1;373(Pt 3):767-74. [PubMed:12741957]
  4. Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. [PubMed:12874005]
  5. Volk EL, Schneider E: Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43. [PubMed:14500392]
  6. Suzuki K, Doki K, Homma M, Tamaki H, Hori S, Ohtani H, Sawada Y, Kohda Y: Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009 Jan;67(1):44-9. doi: 10.1111/j.1365-2125.2008.03303.x. Epub 2008 Nov 17. [PubMed:19076159]
  7. Hou YX, Li CZ, Palaniyandi K, Magtibay PM, Homolya L, Sarkadi B, Chang XB: Effects of putative catalytic base mutation E211Q on ABCG2-mediated methotrexate transport. Biochemistry. 2009 Sep 29;48(38):9122-31. doi: 10.1021/bi900675v. [PubMed:19691360]
  8. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995]
  9. Dai CL, Liang YJ, Wang YS, Tiwari AK, Yan YY, Wang F, Chen ZS, Tong XZ, Fu LW: Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18. [PubMed:19232821]
Kind
Protein
Organism
Humans
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
  1. Sun W, Wu RR, van Poelje PD, Erion MD: Isolation of a family of organic anion transporters from human liver and kidney. Biochem Biophys Res Commun. 2001 May 4;283(2):417-22. [PubMed:11327718]
  2. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. [PubMed:9650585]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H: Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. Epub 2007 May 2. [PubMed:17475902]
Kind
Protein
Organism
Humans
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
  1. Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R, Adachi H, Fujiwara K, Okabe M, Suzuki T, Nunoki K, Sato E, Kakyo M, Nishio T, Sugita J, Asano N, Tanemoto M, Seki M, Date F, Ono K, Kondo Y, Shiiba K, Suzuki M, Ohtani H, Shimosegawa T, Iinuma K, Nagura H, Ito S, Matsuno S: LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99. [PubMed:11375950]
  2. van de Steeg E, van der Kruijssen CM, Wagenaar E, Burggraaff JE, Mesman E, Kenworthy KE, Schinkel AH: Methotrexate pharmacokinetics in transgenic mice with liver-specific expression of human organic anion-transporting polypeptide 1B1 (SLCO1B1). Drug Metab Dispos. 2009 Feb;37(2):277-81. doi: 10.1124/dmd.108.024315. Epub 2008 Nov 20. [PubMed:19022939]
Kind
Protein
Organism
Humans
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
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [PubMed:14993604]
Details
21. Folate transporter 1
Kind
Protein
Organism
Humans
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
  1. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID: Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. 2006 Dec 1;127(5):917-28. [PubMed:17129779]
Kind
Protein
Organism
Humans
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
  1. Sharma S, Das M, Kumar A, Marwaha V, Shankar S, Aneja R, Grover R, Arya V, Dhir V, Gupta R, Kumar U, Juyal RC, B K T: Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians. Pharmacogenet Genomics. 2008 Dec;18(12):1041-9. [PubMed:19093297]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Methotrexate binding
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
FOLR2
Uniprot ID
P14207
Uniprot Name
Folate receptor beta
Molecular Weight
29279.31 Da
References
  1. Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26. [PubMed:24284432]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26. [PubMed:24284432]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
L-proline transmembrane transporter activity
Specific Function
Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recog...
Gene Name
SLC36A1
Uniprot ID
Q7Z2H8
Uniprot Name
Proton-coupled amino acid transporter 1
Molecular Weight
53075.045 Da
References
  1. Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26. [PubMed:24284432]

Drug created on June 13, 2005 07:24 / Updated on November 25, 2020 08:52

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