19835-03-1Relevant academic research and scientific papers
Discovery of potent and selective PKC-θ inhibitors
Cywin, Charles L.,Dahmann, Georg,Prokopowicz III, Anthony S.,Young, Erick R.R.,Magolda, Ronald L.,Cardozo, Mario G.,Cogan, Derek A.,DiSalvo, Darren,Ginn, John D.,Kashem, Mohammed A.,Wolak, John P.,Homon, Carol A.,Farrell, Thomas M.,Grbic, Heather,Hu, Hanbo,Kaplita, Paul V.,Liu, Lisa H.,Spero, Denice M.,Jeanfavre, Deborah D.,O'Shea, Kathy M.,White, Della M.,Woska Jr., Joseph R.,Brown, Maryanne L.
, p. 225 - 230 (2007/10/03)
An uHTS campaign was performed to identify selective inhibitors of PKC-θ. 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-θ 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.
