Structure-based virtual screening approach to the discovery of phosphoinositide 3-kinase alpha inhibitors

Hwangseo Park; Hwanho Choi; Seunghee Hong; Donghee Kim; Dal-Seok Oh; Sungwoo Hong

doi:10.1016/j.bmcl.2011.02.015

Structure-based virtual screening approach to the discovery of phosphoinositide 3-kinase alpha inhibitors

Bioorg Med Chem Lett. 2011 Apr 1;21(7):2021-4. doi: 10.1016/j.bmcl.2011.02.015. Epub 2011 Feb 26.

Authors

Hwangseo Park¹, Hwanho Choi, Seunghee Hong, Donghee Kim, Dal-Seok Oh, Sungwoo Hong

Affiliation

¹ Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea. dsoh@kiom.re.kr

PMID: 21354792
DOI: 10.1016/j.bmcl.2011.02.015

Abstract

Phosphoinositide 3-kinase alpha (PI3Kα) has proved to be an attractive target for the development of therapeutics for the treatment of cancer. Herein we report a successful application of the structure-based virtual screening to identify the novel inhibitors of PI3Kα. These inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with IC(50) values ranging from 20 to 40 μM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of PI3Kα are addressed in detail.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Binding Sites
Drug Discovery*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Models, Molecular
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Phosphoinositide-3 Kinase Inhibitors
Adenosine Triphosphate