Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax.
Hannah M King, Sandeep Rana, Sydney P Kubica, Jayapal Reddy Mallareddy, Smitha Kizhake, Edward L Ezell, Muhammad Zahid, Michael J Naldrett, Sophie Alvarez, Henry C-H Law, Nicholas T Woods, Amarnath Natarajan
Bioorganic & medicinal chemistry letters 2021 Jul 01Cyclin-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. Copyright © 2021 Elsevier Ltd. All rights reserved.
Citation
Hannah M King, Sandeep Rana, Sydney P Kubica, Jayapal Reddy Mallareddy, Smitha Kizhake, Edward L Ezell, Muhammad Zahid, Michael J Naldrett, Sophie Alvarez, Henry C-H Law, Nicholas T Woods, Amarnath Natarajan. Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax. Bioorganic & medicinal chemistry letters. 2021 Jul 01;43:128061
Mesh Tags
Substances
PMID: 33895280
View Full Text
