Trimetrexate glucuronate is a nonclassical antifolate introduced in the
U.S.A. and Canada as second-line therapy for the treatment of Pneumocystis carinii
pneumonia (PCP) and toxoplasmosis in AIDS patients who are refractory or
intolerant to co-trimoxazole therapy. Trimetrexate glucuronate is reportedly to be in
clinical trials for the treatment of several types of cancer including colorectal,
gastric, pancreas, prostate, bladder, lung, breast, head, and neck cancers. It is
also in early clinical trials for topical use in treating psoriasis and as an oral drug to
treat rheumatoid arthritis. The mechanism of action of trimetrexate glucuronate is
via inhibition of the enzyme dihydrofolate reductase which mediates the reduction of
dihydrofolate to tetrahydrofolic acid and results in disruption of DNA, RNA and
protein synthesis, with consequent cell death. Due to its toxicity to bone marrow
and the GI tract, trimetrexate glucuronate must be concurrently administered with
leucovorin as a rescue agent.
용도
Antineoplastic.
생물학적 활성
Potent lipophilic inhibitor of dihydrofolate reductase (DHFR) that displays antineoplastic and antiprotozoal properties. Inhibits protozoal, bacterial and human DHFR with IC 50 values of 1.4, 6.1 and 3.2 nM respectively. Affects G 1 /S phase cell cycle progression.
