[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"notifications-list":3,"$f5dd09t0d1hcb":5},{"data":4},[],{"data":6,"error":11},{"id":7,"documentId":8,"slug":9,"name":10,"medical_code":11,"short_description":12,"alternate_name":11,"disambiguating_description":11,"citations":13,"drugs":32,"specialties":41,"cover":11},829,"cq922kn0exh7lir3y44t8cei","dihydrofolate-reductase-inhibitors","Dihydrofolate Reductase Inhibitors",null,"Dihydrofolate reductase reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate using NADPH - the single step of that sub-pathway. It is the key enzyme of folate metabolism, catalysing a reaction essential for de novo glycine and purine synthesis and for DNA precursor synthesis, and contributing to nuclear and mitochondrial de novo thymidylate biosynthesis. Drugs in this class inhibit that enzyme, so the target cell loses its supply of reduced folate and of the nucleotides built from it. The enzyme is present in both host and microbe: UniProt carries the human DHFR and the Escherichia coli folA entries, and records E. coli strains resistant to trimethoprim and to methotrexate. As MED-RT populates the class its members are the antifolate cytotoxics and antiprotozoals - methotrexate, pemetrexed, pralatrexate, trimetrexate, proguanil and lamotrigine; trimethoprim and pyrimethamine are filed one level up, in Folic Acid Metabolism Inhibitors. FDA's veterinary antimicrobial ranking gives the row 'sulfonamides, dihydrofolate reductase inhibitors, and combinations' two rankings, not one: critically important, because trimethoprim-sulfamethoxazole is one of limited available therapies for serious infections due to Nocardia species and Listeria monocytogenes, and important for sulfonamides alone, which are used to treat non-serious infections for which drugs from more than a few antimicrobial classes are available.",[14,20,24,28],{"claims":15,"source":16,"licence":17,"source_url":18,"retrieved_at":19},"Human DHFR: reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate in an NADPH-dependent manner; key enzyme in folate metabolism; essential reaction for de novo glycine and purine synthesis and for DNA precursor synthesis; contribution to nuclear and mitochondrial de novo thymidylate biosynthesis; PATHWAY step 1\u002F1.","UniProtKB P00374","not stated on source page","https:\u002F\u002Frest.uniprot.org\u002Funiprotkb\u002FP00374.json","2026-09-19",{"claims":21,"source":22,"licence":17,"source_url":23,"retrieved_at":19},"E. coli folA: same catalytic reaction and pathway step; MISCELLANEOUS records a trimethoprim-resistant strain and a methotrexate-resistant strain.","UniProtKB P0ABQ4","https:\u002F\u002Frest.uniprot.org\u002Funiprotkb\u002FP0ABQ4.json",{"claims":25,"source":26,"licence":17,"source_url":27,"retrieved_at":19},"The row 'Sulfonamides, dihydrofolate reductase inhibitors, and combinations' carries both C - 'Trimethoprim-Sulfamethoxazole is one of limited available therapies for serious infections due to Nocardia species, L. monocytogenes' - and I - 'Sulfonamides are used to treat non-serious infections for which drugs from more than a few antimicrobial classes are available.'","FDA CVM Guidance for Industry #152, Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern (ranking table)","https:\u002F\u002Fwww.fda.gov\u002Fmedia\u002F69949\u002Fdownload",{"claims":29,"source":30,"licence":17,"source_url":31,"retrieved_at":19},"Class membership: lamotrigine, methotrexate, pemetrexed, pralatrexate, proguanil, trimetrexate - and no trimethoprim or pyrimethamine.","RxNav RxClass class members (MED-RT), classId N0000000191","https:\u002F\u002Frxnav.nlm.nih.gov\u002FREST\u002Frxclass\u002FclassMembers.json?classId=N0000000191&relaSource=MEDRT&rela=has_MoA",[33,37],{"id":34,"documentId":35,"slug":36,"name":36,"active_ingredient":11,"dosage_form":11,"administration_route":11},1789,"anhpzzdizrhu7vcu84ztcuuy","pyrimethamine",{"id":38,"documentId":39,"slug":40,"name":40,"active_ingredient":11,"dosage_form":11,"administration_route":11},1837,"rhefcalcgcbxa9sxblkynjkm","trimethoprim",[]]