Aminopyrazole Based CDK9 PROTAC Sensitizes Pancreatic Cancer Cells to Venetoclax

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2021 Apr 25

PMID 33895280

Citations 18

Authors

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

Affiliations

Soon will be listed here.

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 (DC = 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.

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