SAR-020106是一种ATP竞争性的、选择性好的CHK1抑制剂，IC50为13.3nM。SAR-020106对CHK2具有良好的选择性。SAR-020106在几种结肠肿瘤细胞系中以p53依赖性方式将Gemcitabine和SN38的细胞杀伤力提高了3.0到29倍。SAR-020106可通过选择抗癌药物增强抗肿瘤活性。
货号:ajcx31448
CAS:1184843-57-9
分子式:C19H19ClN6O
分子量：382.85
溶解度:DMSO: 5 mg/mL (13.06 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC50 of 13.3 nM for human CHK1. SAR-020106 shows excellent selectivity over CHK2. SAR-020106 significantly enhances the cell killing of Gemcitabine and SN38 by 3- to 29-fold in several colon tumor lines and in a p53-dependent fashion. SAR-020106 can enhance antitumor activity with selected anticancer drugs[1][2].

SAR-020106 (0.1-1 μM; 23 hours) abrogates an Etoposide-induced S and G2 arrest[1].SAR-020106 is capable of abrogating Etoposide-induced cell cycle arrest with an IC50 of 55 nM and 91 nM in HT29 and SW620 cells, respectively. SAR-020106 is relatively nontoxic with a GI50 of 0.48 μM in HT29 and 2 μM in SW620, resulting in an activity index of 8.7 and 22, respectively. SAR-020106 inhibits cytotoxic drug-induced autophosphorylation of CHK1 at S296 and blocks the phosphorylation of CDK1 at Y15 in a dose-dependent fashion[1].

SAR-020106 (40 mg/kg; i.p.; administered on days 0, 1, 7, 8, 14, and 15) in combination with Irinotecan potentiates the antitumor activity in SW620 xenografts[1]. Animal Model: Nude mice bearing SW620 xenograft tumors[1]

[1]. Walton MI, et al. The preclinical pharmacology and therapeutic activity of the novel CHK1 inhibitor SAR-020106. Mol Cancer Ther. 2010;9(1):89-100. [2]. Reader JC, et al. Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing. J Med Chem. 2011;54(24):8328-8342.