Pelitrexol (AG 2037) is an inhibitor of glycinamide ribonucleotide formyltransferase ( GARFT ), a purine biosynthetic enzyme. Pelitrexol also inhibits mTORC1 by reducing GTP-bound Rheb level, a mTORC1 obligate activator. Pelitrexol shows robust tumor growth suppression in mice
In Vitro
Pelitrexo (150 nM; 24 h) profoundly inhibits mTORC1 activity by reducing intracellular guanine nucleotides level as well as GTP-bound Rheb protein level in A549 cells. Pelitrexo (0-1000 mM; 16 h) strongly inhibits the phosphorylation level of ribosomal protein S6 (S6RP), S6K1, and Chk1 in a dose-dependent manner in NCI-H460 cells. Pelitrexo (100 nM; 48 h) arrests cell cycle at G1 phase in NCI-H460 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Cycle AnalysisCell Line: NCI-H460 NSCLC Concentration: 100 nM Incubation Time: 4, 8, 24, 48 hours Result: Resulted 63% cells accumulation in G1 phase of the cell cycle. Cell Cycle AnalysisCell Line: NCI-H460 NSCLC Concentration: 0, 10, 30, 100, 300, 1000 nM Incubation Time: 16 hours Result: Inhibits the level of p-S6RP, p-S6K1, and p-Chk1.
In Vivo
Pelitrexo (10 mg/kg, 20 mg/kg; i.p.; every 4 days for 3 weeks) provokes both mTORC1 inhibition and robust tumor growth suppression in mice bearing nonsmall-cell lung cancer (NSCLC) xenografts . Pelitrexo (20 mg/kg; i.p.; every 4 days for 3 weeks) inhibits GARFT-dependent purine biosynthesis and blocks mTORC1 function . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Xenograft model of nonsmall-cell lung cancer (NSCLC) in mice Dosage: 10 mg/kg, 20 mg/kg Administration: Intraperitoneal injection; every 4 days for 3 weeks for group 1; administrated at 1, 4, 7 days for group 2 Result: Inhibited tumor growth by 64% and 69% at 10 mg/kg and 20 mg/kg, respectively in group 1. Inhibited mTORC1-dependent phosphorylation of S6K1, S6RP and CAD at 20 mg/kg in group 2.
Form:Solid
IC50& Target:GARFT
