SAR-020106

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]. In Vitro: 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]. In Vivo: 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].