Pelitrexol, GAR 转化酶抑制剂

小分子

培利曲索

Pelitrexol (USAN/INN) | (2S)-2-(((5-(2-((6S)-2-Amino-4-oxo-1,4,5,6,7,8-hexahydropyrido(2,3-d)pyrimidin-6-yl)ethyl)-4-methylthiophen-2-yl)carbonyl)amino)pentanedioic acid | AG-2038 | PELITREXOL [INN] | NSC767745 | NSC-767745 | Pelitrexol [USAN] | (2S)-2-[[

Pelitrexol

P649403-5mg

5mg

≥98%

-20°C储存

超低温冰袋运输

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

Pelitrexol (AG 2037) 是嘌呤生物合成酶甘氨核糖核苷酸甲酰转移酶（GARFT）的抑制剂。Pelitrexol 还能通过降低 GTP 结合的 Rheb 水平抑制 mTORC1，Rheb 是 mTORC1 的强制性激活剂。哌立曲醇显示出强大的肿瘤生长能力。

446022-33-9

C20H25N5O6S

463.51 g/mol

135431074

CC1=C(SC(=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)O)CC[C@H]2CC3=C(NC2)N=C(NC3=O)N

(2S)-2-[[5-[2-[(6S)-2-amino-4-oxo-5,6,7,8-tetrahydro-3H-pyrido[2,3-d]pyrimidin-6-yl]ethyl]-4-methylthiophene-2-carbonyl]amino]pentanedioic acid

1S/C20H25N5O6S/c1-9-6-14(18(29)23-12(19(30)31)3-5-15(26)27)32-13(9)4-2-10-7-11-16(22-8-10)24-20(21)25-17(11)28/h6,10,12H,2-5,7-8H2,1H3,(H,23,29)(H,26,27)(H,30,31)(H4,21,22,24,25,28)/t10-,12-/m0/s1

QXOPTIPQEVJERB-JQWIXIFHSA-N

CC1=C(SC(=C1)C(=O)NC(CCC(=O)O)C(=O)O)CCC2CC3=C(NC2)N=C(NC3=O)N

135431074

446022-33-9

pelitrexol

DMSO : 25 mg/mL (53.94 mM; Need ultrasonic)

6

9

9

463.153 Da

463.153 Da

211.000 Ų

32

0

859.000

0

1

0.700

0.7

抑制剂

GAR 转化酶抑制剂