title: Structure-based virtual screening approach to the discovery of phosphoinositide 3-kinase alpha inhibitors.
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.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea. dsoh@kiom.re.kr
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Hwanho
authors.initials: H
authors.lastname: Choi
authors.forename: Seunghee
authors.initials: S
authors.lastname: Hong
authors.forename: Donghee
authors.initials: D
authors.lastname: Kim
authors.forename: Dal-Seok
authors.initials: DS
authors.lastname: Oh
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Hong
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000255:Adenosine Triphosphate; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors