Development of single and mixed isoform selectivity PI3Kδ inhibitors by targeting Asn836 of PI3Kδ

Michelle S. Miller, Simon J. Mountford, Jo-Anne Pinson, Zhaohua Zheng, Marco Künzli, Vanit Patel, Simon J. Hogg, Jake Shortt, Ian G. Jennings, Philip E. Thompson

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

A series of PI3Kδ inhibitors derived from the pan-PI3K inhibitor ZSTK474 was prepared that target a non-conserved region of the catalytic site. Dependent upon the substituents present, these analogues show different levels of isoform selectivity and sensitivity to the mutation N836D in PI3Kδ. As a marker of ‘on-target’ activity and permeability, a selection of the most potent PI3Kδ inhibitors were shown to inhibit pAkt production in the Nawalma Burkitt lymphoma cell line.

Original languageEnglish
Pages (from-to)4790-4794
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number19
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • Isoform selectivity
  • Leukemia
  • Lymphoma
  • PI3 kinase inhibitor

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