From PIM1 to PI3Kδ via GSK3β: Target hopping through the kinome

Henley, Zoë A., Bax, Benjamin D. ORCID: https://orcid.org/0000-0003-1940-3785, Inglesby, Laura M., Champigny, Aurélie, Gaines, Simon, Faulder, Paul, Le, Joelle, Thomas, Daniel A., Washio, Yoshiaki and Baldwin, Ian R. 2017. From PIM1 to PI3Kδ via GSK3β: Target hopping through the kinome. ACS Medicinal Chemistry Letters 8 (10) , pp. 1093-1098. 10.1021/acsmedchemlett.7b00296

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Abstract

Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the treatment of inflammatory diseases. Initial optimization of a 3-substituted indazole hit compound targeting the kinase PIM1 focused on improving selectivity over GSK3β through consideration of differences in the ATP binding pockets. Continued kinase cross-screening showed PI3Kδ activity in a series of 4,6-disubstituted indazole compounds, and subsequent structure–activity relationship exploration led to the discovery of an indole-containing lead compound as a potent PI3Kδ inhibitor with selectivity over the other PI3K isoforms.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Publisher:	American Chemical Society
ISSN:	1948-5875
Date of First Compliant Deposit:	8 May 2018
Date of Acceptance:	5 September 2017
Last Modified:	23 Oct 2022 13:38
URI:	https://orca.cardiff.ac.uk/id/eprint/111253

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