SAR-020106

SAR-020106 is a potent, ATP-competitive, and selective CHK1 inhibitor with an IC50 of 13.3 nmol/L on the isolated human enzyme.SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC (50) of 13.3 nmol/L on the isolated human enzyme. This compound abrogates an etoposide-induced G (2) arrest with an IC (50) of 55 nmol/L in HT29 cells, and significantly enhances the cell killing of gemcitabine and SN38 by 3.0- to 29-fold in several colon tumor lines in vitro and in a p53-dependent fashion. Biomarker studies have shown that SAR-020106 inhibits cytotoxic drug-induced autophosphorylation of CHK1 at S296 and blocks the phosphorylation of CDK1 at Y15 in a dose-dependent fashion both in vitro and in vivo. Cytotoxic drug combinations were associated with increased gammaH2AX and poly ADP ribose polymerase cleavage consistent with the SAR-020106-enhanced DNA damage and tumor cell death. Irinotecan and gemcitabine antitumor activity was enhanced by SAR-020106 in vivo with minimal toxicity. SAR-020106 represents a novel class of CHK1 inhibitors that can enhance antitumor activity with selected anticancer drugs in vivo and may therefore have clinical utility.SAR-020106 potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.

1184843-57-9

>98% (HPLC)

In Vitro: DMSO : 5 mg/mL (13.06 mM)

C[C@H] (CN (C) C) Oc1nc (Nc2cc3cccc (Cl) c3cn2) cnc1C#N

C19H19ClN6O

382.85

Storage temperature: -20°C. Stability: ≥ 2 years