trimetrexate

Ligand id: 7613

Name: trimetrexate

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 117.54
Molecular weight 369.18
XLogP 1.45
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Trimetrexate was originally approved by the US FDA in 1993, but use of this drug has since been discontinued. Trimetrexate was used in combination with folinic acid to treat moderate to severe Pneumocystis carinii pneumonia (PCP) in patients with compromised immune systems [3]. It was also used to treat some types of cancer including colon cancer [5] and investigated as a treatment for leiomyosarcoma [4] and methotrexate resistant skin lymphoma [2].
Mechanism Of Action and Pharmacodynamic Effects
Trimetrexate inhibits dihydrofolate reductase (DHFR) [6] across many species. Inhibition of this enzyme reduces active coenzyme tetrahydrofolate and folic acid supplies within cells (be they host cells or infection causing microbes). This leads to reduced thymidylate biosynthesis, and inhibition of folate-dependent formyltransferases. The net effect is disruption of DNA, RNA, and protein synthesis and this leads to cell death.