An interesting innovation project has resulted from the exploration of alternative kinase inhibition modes. Expert in-house knowledge and an efficient platform for development with our partners led to potent CDK8 inhibitors with long residence times.
Mercachem and ProQinase developed proprietary scaffolds with a pre-engineered binding kinetics signature. Screening hits were further developed into inhibitors with excellent biochemical potency, cell-based efficacy in the nanomolar range and long residence times (>10 h). Frontrunner compounds were progressed into in vivo studies, resulting in significant tumor growth inhibition in both mouse and rat xenograft models. Additionally, clear in vivo target engagement was demonstrated in rats.