Lometrexol

Lometrexol (DDATHF), an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) but do not induce detectable levels of DNA strand breaks. Lometrexol can further inhibit de novo purine synthesis, causing abnormal cell proliferation and apoptosis, even cell cycle arrest. Lometrexol has anticancer activity. Lometrexol also is a potent human Serine hydroxymethyltransferase1/2 (hSHMT1/2) inhibitor^[1][2][3]. In Vitro:Lometrexol (DDATHF) binds tightly to GART, resulting in a rapid and prolonged depletion of intracellular purine ribonucleotides^[3].
Lometrexol (1-30 μM; 2-10 hours) induces rapid and complete growth inhibition in L1210 cells^[3].
Lometrexol (1 μM; 2-24 hours) induces cell cycle arrest in murine leukemia L1210 cells^[3].
In Vivo:Lometrexol (DDATHF; i.p.; 15-60 mg/kg; on gestation day 7.5) induces neural tube defects (NTDs) by disturbing purine metabolism and increases the rate of embryonic resorption and growth retardation in a dose-dependent manner^[1].
Lometrexol (i.p.; 40 mg/kg; on gestation day 7.5) decreases glycinamide ribonucleotide formyl transferase (GARFT) activity and Changes of ATP, GTP, dATP and dGTP levels^[1].
Lometrexol (i.p.; 40 mg/kg; on gestation day 7.5) induces abnormal proliferation and apoptosis exist in neural tube defects (NTDs)^[1].