Abstract
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
Current Medicinal Chemistry
Title: Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-Kinase (PI3K) Inhibitors
Volume: 18 Issue: 18
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:
Keywords: PI3K, inhibitor, p110α, p110β, p110δ, p110ggr;, mTOR, cancer, inflammation, cardiovascular, phosphoinositide
Abstract: 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.
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J. Shuttleworth S., A. Silva F., R.L. Cecil A., D. Tomassi C., J. Hill T., I. Raynaud F., A. Clarke P. and Workman P., Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-Kinase (PI3K) Inhibitors, Current Medicinal Chemistry 2011; 18 (18) . https://dx.doi.org/10.2174/092986711796011229
DOI https://dx.doi.org/10.2174/092986711796011229 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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