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Pelitrexol

CAS No. : 446022-33-9

產(chǎn)品活性：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.

研究領(lǐng)域：Cell Cycle/DNA Damage

作用靶點(diǎn)：Antifolate

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.

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.

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