Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge


Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-Kinase (PI3K) Inhibitors

Author(s): S. J. Shuttleworth, F. A. Silva, A. R.L. Cecil, C. D. Tomassi, T. J. Hill, F. I. Raynaud, P. A. Clarke and P. Workman

Affiliation: Karus Therapeutics Ltd., Southampton Science Park, 2 Venture Road, Southampton, SO16 7NP, UK.


The phosphoinositide 3-kinases (PI3Ks) constitute an important family of lipid kinase enzymes that control a range of cellular processes through their regulation of a network of signal transduction pathways, and have emerged as important therapeutic targets in the context of cancer, inflammation and cardiovascular diseases. Since the mid-late 1990s, considerable progress has been made in the discovery and development of small molecule ATP-competitive PI3K inhibitors, a number of which have entered early phase human trials over recent years from which key clinical results are now being disclosed. This review summarizes progress made to date, primarily on the discovery and characterization of class I and dual class I/IV subtype inhibitors, together with advances that have been made in translational and clinical research, notably in cancer.

Keywords: PI3K, inhibitor, p110α, p110β, p110δ, p110ggr;, mTOR, cancer, inflammation, cardiovascular, phosphoinositide

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Article Details

Page: [2686 - 2714]
Pages: 29
DOI: 10.2174/092986711796011229