SAR-020106 (C007B-272587)

InformationSAR-020106 is an ATP-competitive, potent, and selectiveCHK1inhibitor with an IC50 of 13.3 nM.TargetsChk1 (Cell-free assay) 13.3 nMIn vitroSAR-020106 abrogates an etoposide-induced G2 arrest with an IC50 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. SAR-020106 inhibits cytotoxic drug-induced autophosphorylation of CHK1 at S296 and blocks the phosphorylation of CDK1 at Y15 in a dose-dependent fashion.In vivoSAR-020106 can enhance the antitumor effects of both irinotecan and gemcitabine in vivo with appropriate biomarker changes and minimal toxicity. Although having minimal oral bioavailability in mice (F = 5%), distribution of SAR-020106 following i.p. dosing (40 mg/kg) was sufficient to inhibit CHK1 in the tumors, as shown by inhibition of the irinotecan-induced CHK1 pS296 autophosphorylation. At doses giving inhibition of CHK1 activity the selective CHK1 inhibitor SAR-020106 showed no single agent activity in the SW620 xenograft model, and tumors grew at similar rates to the vehicle-treated controls. When dosed (i.p.) in combination with irinotecan, SAR-020106 was observed to potentiate the antitumor activity of the genotoxic drug in the SW620 xenograft model.Cell Research(from reference)Cell lines：SW620 colon cancer cells Concentrations：5 μM Incubation Time：24 h.

Specifications and Purity: ≥97%

Molecular Formula: C19H19ClN6O

Molecular Weight: 382.85

PubChem CID: 44203948

Isomeric SMILES: C[C@H](CN(C)C)OC1=NC(=CN=C1C#N)NC2=NC=C3C(=C2)C=CC=C3Cl