Class 1 PI3K clinical candidates and recent inhibitor design strategies: a medicinal chemistry perspective

Garces, Aimie E.; Stocks, Michael J.

Abstract

Phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate the 3-OH of the inositol ring of phosphoinositides, and deregulation of this pathway has implications in many diseases. The search for novel PI3K inhibitors has been at the forefront of academic and industrial medicinal chemistry with over 600 medicinal chemistry-based publications and patents appearing to date, leading to 38 clinical candidates and the launch of two drugs, idelalisib in 2014 and copanlisib in 2017. This Perspective will discuss medicinal chemistry design approaches to novel isoform-selective inhibitors through consideration of brief case histories of compounds that have progressed into clinical development or that have revealed new structural motifs in this highly competitive area of research.

Citation

Garces, A. E., & Stocks, M. J. (2019). Class 1 PI3K clinical candidates and recent inhibitor design strategies: a medicinal chemistry perspective. Journal of Medicinal Chemistry, 62(10), 4815-4850. https://doi.org/10.1021/acs.jmedchem.8b01492

• Journal Article Type: Article
• Acceptance Date: Dec 24, 2018
• Online Publication Date: Dec 24, 2018
• Publication Date: May 23, 2019
• Deposit Date: Jan 3, 2019
• Publicly Available Date: Dec 25, 2019
• Journal: Journal of Medicinal Chemistry
• Print ISSN: 0022-2623
• Electronic ISSN: 1520-4804
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 62
• Issue: 10
• Pages: 4815-4850
• DOI: https://doi.org/10.1021/acs.jmedchem.8b01492
• Keywords: Molecular Medicine; Drug Discovery
• Public URL: https://nottingham-repository.worktribe.com/output/1441736
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01492
• Contract Date: Jan 3, 2019