title: Targeting the hydrophobic region of Hsp90's ATP binding pocket with novel 1,3,5-triazines.
abstract: Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an important role in regulating the maturation and stabilization of many oncogenic proteins. In an attempt to discover a new class of Hsp90 inhibitors, a series of 1,3,5-triazine compounds were rationally designed, synthesized, and their biological activities were evaluated. Compound 3b was found to degrade Hsp90's client proteins of Her2, Met and Akt and to induce the expression level of Hsp70. The binding mode of 3b in the ATP-binding site of Hsp90 was predicted by the molecular docking.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, South Korea.
authors.forename: Taeho
authors.initials: T
authors.lastname: Lee
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Seo
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D011485:Protein Binding; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D014227:Triazines; D000255:Adenosine Triphosphate
keywords: Cancer; Hsp90; Molecular docking; Structure-based design; Triazines