SAR-020106

SAR-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

Chk1 Selective Inhibitors

Specifications & Purity: SAR-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

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

Storage Temperature: Store at -20°C

Shipped in: Ice chest + Ice pads

UPC:

51442437

Weight:

1.06 Ounces

HazmatClass:

Yes

Quantity:

1

Unit of Measurement:

EA

WeightUOM:

LB

MPN:

S413824-1mg

Country of Origin:

China

CAS:

1184843-57-9

Product Size:

1mg

Harmonized Tariff Code:

2931.90.90