Folic Acid Antagonists

Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)
DrugDrug NameDrug Indication
DB00205PyrimethamineFor the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine
DB00250DapsoneFor the treatment and management of leprosy and dermatitis herpetiformis.
DB00293RaltitrexedFor the treatment of malignant neoplasm of colon and rectum
DB01157TrimetrexateFor use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer.
DB04655MetoprineNot Available
DB06358IclaprimInvestigated for use/treatment in bacterial infection, skin infections/disorders, obesity, liver disease, kidney disease, and pneumonia.
DB08878AminopterinPrior to its withdrawal, aminopterin was initially used in the treatment of childhood leukemia; specifically to induce remissions. Later, aminopterin was used off-label in the United States to treat psoriasis, yielding dramatic lesion clearing. Aminopterin was later supplanted by methotrexate for treating cancer because of its better therapeutic index. Aminopterin (as well as methotrexate) has also been explored for use as an abortifacient. However, their association with severe congenital malformations and teratogenic effects have become known as fetal aminopterin syndrome.
DB12769LometrexolNot Available
DB12912NolatrexedNot Available
DB13795BrodimoprimNot Available
DB00440TrimethoprimFor the treatment of urinary tract infections, uncomplicated pyelonephritis (with sulfamethoxazole) and mild acute prostatitis. May be used as pericoital (with sulfamethoxazole) or continuous prophylaxis in females with recurrent cystitis. May be used as an alternative to treat asymptomatic bacteriuria during pregnancy (only before the last 6 weeks of pregnancy). Other uses include: alternative agent in respiratory tract infections (otitis, sinusitus, bronchitis and pneumonia), treatment of Pneumocystis jirovecii pneumonia (acute or prophylaxis), Nocardia infections, and traveller's diarrhea.
DB00563MethotrexateMethotrexate oral solution is indicated for pediatric acute lymphoblastic leukemia and pediatric polyarticular juvenile idiopathic arthritis.[L7144] Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis.[L7147,L7150] 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.[L7180] It is also used in the maintenance of acute lymphocytic leukemia.[L7180] Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma.[L7180]
DB00642PemetrexedUsed in combination with cisplatin for the treatment of malignant pleural mesothelioma in adults whose disease is unresectable or who otherwise are not candidates for potentially curative surgery. Also used as a monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy
DB06813PralatrexateTreatment of relapsed or refractory peripheral T-cell lymphoma.
DB01131ProguanilFor the causal prevention and suppression of malaria caused by susceptible strains of P. falciparum and other species of Plasmodium found in some geographical areas of the world.
DB03695PiritreximNot Available
DB14763CycloguanilNot Available
DrugDrug NameTargetType
DB00205PyrimethamineBifunctional dihydrofolate reductase-thymidylate synthasetarget
DB00205PyrimethamineDihydrofolate reductasetarget
DB00205PyrimethamineCytochrome P450 2C8enzyme
DB00205PyrimethamineBeta-hexosaminidase subunit betatarget
DB00205PyrimethamineMultidrug and toxin extrusion protein 1transporter
DB00205PyrimethamineMultidrug and toxin extrusion protein 2transporter
DB00250DapsoneInactive dihydropteroate synthase 2target
DB00250DapsoneDihydropteroate synthase 1target
DB00250DapsoneCytochrome P450 2C9enzyme
DB00250DapsoneCytochrome P450 2E1enzyme
DB00250DapsoneCytochrome P450 3A4enzyme
DB00250DapsoneDimethylaniline monooxygenase [N-oxide-forming] 3enzyme
DB00250DapsoneProstaglandin G/H synthase 1enzyme
DB00250DapsoneProstaglandin G/H synthase 2enzyme
DB00250DapsoneCytochrome P450 2C8enzyme
DB00250DapsoneCytochrome P450 2C19enzyme
DB00250DapsoneArylamine N-acetyltransferase 2enzyme
DB00250DapsoneCytochrome P450 3A5enzyme
DB00250DapsoneCytochrome P450 3A7enzyme
DB00250DapsoneMyeloperoxidaseenzyme
DB00250DapsoneCytochrome P450 2C18enzyme
DB00293RaltitrexedThymidylate synthasetarget
DB00293RaltitrexedFolylpolyglutamate synthase, mitochondrialtarget
DB01157TrimetrexateDihydrofolate reductasetarget
DB04655MetoprineHistamine N-methyltransferasetarget
DB06358IclaprimDihydrofolate reductasetarget
DB08878AminopterinProton-coupled folate transportertransporter
DB08878AminopterinDihydrofolate reductaseenzyme
DB12769LometrexolDihydrofolate reductasetarget
DB00440TrimethoprimThymidylate synthasetarget
DB00440TrimethoprimDihydrofolate reductasetarget
DB00440TrimethoprimCytochrome P450 2C8enzyme
DB00440TrimethoprimCytochrome P450 3A4enzyme
DB00440TrimethoprimMultidrug resistance protein 1transporter
DB00440TrimethoprimCytochrome P450 2C9enzyme
DB00440TrimethoprimSolute carrier family 22 member 2transporter
DB00563MethotrexateDihydrofolate reductasetarget
DB00563MethotrexateAldehyde oxidaseenzyme
DB00563MethotrexateMethylenetetrahydrofolate reductaseenzyme
DB00563MethotrexateSerum albumincarrier
DB00563MethotrexateCanalicular multispecific organic anion transporter 2transporter
DB00563MethotrexateMultidrug resistance-associated protein 4transporter
DB00563MethotrexateMultidrug resistance-associated protein 1transporter
DB00563MethotrexateSolute carrier family 22 member 6transporter
DB00563MethotrexateMultidrug resistance-associated protein 7transporter
DB00563MethotrexateSolute carrier family 22 member 8transporter
DB00563MethotrexateCanalicular multispecific organic anion transporter 1transporter
DB00563MethotrexateMultidrug resistance protein 1transporter
DB00563MethotrexateSolute carrier organic anion transporter family member 1A2transporter
DB00563MethotrexateMonocarboxylate transporter 1transporter
DB00563MethotrexateATP-binding cassette sub-family C member 11transporter
DB00563MethotrexateSolute carrier organic anion transporter family member 1B3transporter
DB00563MethotrexateSolute carrier family 22 member 11transporter
DB00563MethotrexateSolute carrier organic anion transporter family member 1C1transporter
DB00563MethotrexateSolute carrier organic anion transporter family member 3A1transporter
DB00563MethotrexateATP-binding cassette sub-family G member 2transporter
DB00563MethotrexateSolute carrier family 22 member 7transporter
DB00563MethotrexateSolute carrier organic anion transporter family member 1B1transporter
DB00563Methotrexate6-phosphogluconate dehydrogenase, decarboxylatingenzyme
DB00563MethotrexateProton-coupled folate transportertransporter
DB00563MethotrexateFolylpolyglutamate synthase, mitochondrialenzyme
DB00563MethotrexateGamma-glutamyl hydrolaseenzyme
DB00563MethotrexateDihydrofolate reductaseenzyme
DB00563MethotrexateThymidylate synthaseenzyme
DB00563MethotrexateBifunctional purine biosynthesis protein PURHenzyme
DB00563MethotrexateSolute carrier organic anion transporter family member 4C1transporter
DB00563MethotrexateFolate transporter 1transporter
DB00563MethotrexateFolate receptor alphatransporter
DB00563MethotrexateCytochrome P450 3A4enzyme
DB00563MethotrexateThymidylate synthasetarget
DB00563MethotrexateBifunctional purine biosynthesis protein PURHtarget
DB00563MethotrexateFolate receptor betatransporter
DB00563MethotrexateSolute carrier family 15 member 1transporter
DB00563MethotrexateProton-coupled amino acid transporter 1transporter
DB00642PemetrexedThymidylate synthasetarget
DB00642PemetrexedDihydrofolate reductasetarget
DB00642PemetrexedTrifunctional purine biosynthetic protein adenosine-3target
DB00642PemetrexedDeoxycytidine kinaseenzyme
DB00642PemetrexedBifunctional purine biosynthesis protein PURHtarget
DB00642PemetrexedEquilibrative nucleoside transporter 1enzyme
DB00642PemetrexedSolute carrier family 22 member 8transporter
DB06813PralatrexateFolylpolyglutamate synthase, mitochondrialenzyme
DB06813PralatrexateDihydrofolate reductasetarget
DB06813PralatrexateThymidylate synthasetarget
DB06813PralatrexateFolate transporter 1transporter
DB01131ProguanilBifunctional dihydrofolate reductase-thymidylate synthasetarget
DB01131ProguanilDihydrofolate reductasetarget
DB01131ProguanilCytochrome P450 2C19enzyme
DB01131ProguanilCytochrome P450 2D6enzyme
DB01131ProguanilCytochrome P450 2C9enzyme
DB03695PiritreximDihydrofolate reductasetarget