Structural bioinformatics analysis predicts superior kinome selectivity of clinical p38 MAPK inhibitor.

Li Xing, Pfizer, Cambridge, USA

PH-797804 is a p38 kinase inhibitor derived from a racemic mixture as the more potent atropisomer. Structural bioinformatics mining of human kinase genome identified a selectivity motif on the kinase hinge. PH-797804 exhibited high specificity against MAPK and large kinase panels, which translated well to cellular systems. Safety was proven in Phase I clinical trials. Efficacy was achieved in certain human disease population.