Biological Activity
SCH900776 is a potent, selective and oral inhibitor of checkpoint kinase1 (Chk1) with an IC50 of 3 nM. It shows 50- and 500-fold selectivity over CDK2 andChk2, respectively.
In Vitro
SCH900776 (300 nM) shows potent inhibitory activities against phosphorylation at ser296-Chk1. SCH900776 (1 μM) causes a 30-fold decrease in the IC50 for hydroxyurea in MDA-MB-231 cells[1]. The Kd value of SCH 900776 for the CHK1 kinase domain is 2 nM. SCH 900776 exhibits an approximate EC50 of 60 nM in cells exposure to hydroxyurea. SCH 900776 induces dose-dependent suppression of CHK1 pS296 and concomitant accumulation of phospho-RPA signal in U2OS cells[2].
In Vivo
SCH 900776 induces the γ-H2AX biomarker at 4 mg/kg (i.p.), and enhances tumor pharmacodynamic and regression responses in A2780 xenograft model. SCH 900776 (16 and 32 mg/kg, i.p.) induces incremental improvements in tumor response. Escalation of SCH 900776 dose to 20 and 50 mg/kg in combination with gemcitabine results in improvements in TTP 10× in the A2780 xenograft systems[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
