lometrexol

Lometrexol is a folate analog antimetabolite and the 6R diastereomer of 5,10-dideazatetrahydrofolate. It acts as an inhibitor of glycinamide ribonucleotide formyltransferase (GARFT), an enzyme essential for the first step in the de novo purine biosynthetic pathway. By inhibiting GARFT, lometrexol disrupts DNA synthesis and arrests cells in the S phase of the cell cycle, leading to inhibition of tumor cell proliferation. Lometrexol has demonstrated activity against tumors resistant to methotrexate and was investigated primarily for various solid tumors including non-small cell lung cancer. Its clinical development was curtailed due to severe toxicities but could be mitigated with folic acid supplementation.

Other names

lometrexolum5,10-dideaza-5,6,7,8-tetrahydrofolic acid5,10-dideazatetrahydrofolate5,10-dideazatetrahydrofolic acid