Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax

Cyclin-dependent kinase 9 (CDK9) is a member of the cyclin-dependent kinase (CDK) family which is involved in transcriptional regulation of several genes, including the oncogene Myc, and is a validated target for pancreatic cancer. Here we report the development of an aminopyrazole based proteolysis targeting chimera (PROTAC 2) that selectively degrades CDK9 (DC50 = 158 +/- 6 nM). Mass spectrometry-based kinome profiling shows PROTAC 2 selectively degrades CDK9 in MiaPaCa2 cells and sensitizes them to Venetoclax mediated growth inhibition.

Automated summary

CDK9, a member of the cyclin-dependent kinase family, is involved in transcriptional regulation. Researchers developed PROTAC 2, a compound that selectively degrades CDK9, sensitizing cells to growth inhibition by Venetoclax.