Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax.

Basic Information

ID: ALA4819106

Journal: Bioorg Med Chem Lett

Title: Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax.

Authors: King HM, Rana S, Kubica SP, Mallareddy JR, Kizhake S, Ezell EL, Zahid M, Naldrett MJ, Alvarez S, Law HC, Woods NT, Natarajan A.

Abstract: 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.

CiteXplore: 33895280

DOI: 10.1016/j.bmcl.2021.128061

Patent ID: ┄

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