3042 T3D3000 Trimetrexate A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. [PubChem] 52128-35-5 5583 C19H23N5O3 369.180090 White powder. 215-217°C 31.4 mg/L Intravenous injection In vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death. Hepatic. Preclinical data strongly suggest that the major metabolic pathway is oxidative O-demethylation, followed by conjugation to either glucuronide or the sulfate. Route of Elimination: Ten to 30% of the administered dose is excreted unchanged in the urine. Half Life: 11 to 20 hours LD50: 62 mg/kg (Intravenous, Mouse) (A308) No indication of carcinogenicity to humans (not listed by IARC). For use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe <i>Pneumocystis carinii</i> pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer. Antibiotic resistance The most common side effects from antibiotics are diarrhea, nausea, vomiting. Fungal infections of the mouth, digestive tract and vagina can also occur with antibiotics In the event of overdose, Trimetrexate should be stopped and leucovorin should be administered at a dose of 40 mg/m2 every 6 hours for 3 days. (L1712) 2009-07-21T20:28:29Z 2014-12-24T20:25:55Z Trimetrexate C11154 119101 Trimetrexate DB01157 TMQ true COC1=CC(NCC2=C(C)C3=C(NC(=N)NC3=N)C=C2)=CC(OC)=C1OC C19H23N5O3 InChI=1S/C19H23N5O3/c1-10-11(5-6-13-16(10)18(20)24-19(21)23-13)9-22-12-7-14(25-2)17(27-4)15(8-12)26-3/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24) InChIKey=NOYPYLRCIDNJJB-UHFFFAOYSA-N 369.4176 369.180089627 Exogenous Solid 2.55 HMDB15288 CHEMBL119 5381 <p>Martin Stogniew, Javad M. Zadei, &#8220;Compositions comprising trimetrexate and methods of their synthesis and use.&#8221; U.S. Patent US6258821, issued January, 1974.</p>