title: A novel class of Hsp90 inhibitors isolated by structure-based virtual screening.
abstract: A novel class of 3-phenyl-2-styryl-3H-quinazolin-4-one Hsp90 inhibitors with in vitro anti-tumor activity are identified by structure-based virtual screening of a chemical database with docking simulations in the N-terminal ATP-binding site, in vitro ATPase assay using yeast Hsp90, and cell-based Her2 degradation assay in a consecutive fashion. These results exemplify the usefulness of the structure-based virtual screening with molecular docking in drug discovery. The structural features responsible for a tight binding of the inhibitors in the active site of Hsp90 are discussed in detail.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Gwangjin-gu, Seoul, Republic of Korea.
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Hahn
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D011799:Quinazolines