Feb 14
Chemistry Department Seminar: Kevin Freeman-Cook '94 (Pfizer)
Phosphorylation of the retinoblastoma protein (RB1) by cyclin-dependent kinases (CDK) 4 and 6 is a critical step which causes cell cycle progression and can lead to cell proliferation. In certain types of cancer, this process is unregulated and can significantly drive tumor growth. Palbociclib, a highly selective inhibitor of CDK4 and 6, significantly improves progression free survival in hormone receptor positive (HR+) HER2 negative breast cancer when combined with an anti-hormonal agent. In anticipation of identifying resistant tumors, we sought to develop new inhibitors that also targeted the related kinase CDK2. This talk will look back at some of the work that led to palbociclib, and then discuss our new approach to discover a selective inhibitor of CDK2, CDK4 and CDK6.