pkc-theta-inhibitor

Description: PKC-theta inhibitor is a novel, potent and selective PKC-theta inhibitor with an IC50 of 12 nM. It was discovered from an uHTS campaign to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2, 4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds.

References: Bioorg Med Chem Lett. 2007 Jan 1; 17(1):225-30.