The guest speaker for the Dec. 4th Chemistry & Biochemistry Colloquium will be Dr. Steven Fletcher. Dr. Fletcher is an Associate Professor in the Department of Pharmaceutical Sciences at the University of Maryland School of Pharmacy.

CDK9 PROTACs: Indirect Downregulation of the Anti-Apoptotic MCL-1 Oncoprotein

Although MCL-1 has been validated as a target in oncology, multiple clinical trials of highly potent and selective MCL-1 inhibitors have failed through the development of cardiotoxicity. We believe this is due to the associated increase in MCL-1 stability. We propose to instead downregulate MCL-1 through the pharmacologic inhibition of CDK9, which is involved in the transcriptional regulation of MCL-1. Moreover, to ensure a sustained downregulation of MCL-1, our strategy invokes the emerging platform of PRoteolysis Targeting Chimeras (PROTACs), wherein the inhibitors that will be described are designed to also degrade the CDK9 protein.