title: Fragment-based identification of Hsp90 inhibitors.
abstract: Heat shock protein 90 (Hsp90) plays a key role in stress response and protection of the cell against the effects of mutation. Herein we report the identification of an Hsp90 inhibitor identified by fragment screening using a high-concentration biochemical assay, as well as its optimisation by in silico searching coupled with a structure-based drug design (SBDD) approach.
authors.affiliation: Evotec, 114 Milton Park, Abingdon, Oxfordshire, OX10 4SA UK.
authors.forename: John J
authors.initials: JJ
authors.lastname: Barker
authors.forename: Oliver
authors.initials: O
authors.lastname: Barker
authors.forename: Roberto
authors.initials: R
authors.lastname: Boggio
authors.forename: Viddhata
authors.initials: V
authors.lastname: Chauhan
authors.forename: Robert K Y
authors.initials: RK
authors.lastname: Cheng
authors.forename: Vincent
authors.initials: V
authors.lastname: Corden
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Courtney
authors.forename: Neil
authors.initials: N
authors.lastname: Edwards
authors.forename: Virginie M
authors.initials: VM
authors.lastname: Falque
authors.forename: Fulvia
authors.initials: F
authors.lastname: Fusar
authors.forename: Mihaly
authors.initials: M
authors.lastname: Gardiner
authors.forename: Estelle M N
authors.initials: EM
authors.lastname: Hamelin
authors.forename: Thomas
authors.initials: T
authors.lastname: Hesterkamp
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichihara
authors.forename: Richard S
authors.initials: RS
authors.lastname: Jones
authors.forename: Owen
authors.initials: O
authors.lastname: Mather
authors.forename: Ciro
authors.initials: C
authors.lastname: Mercurio
authors.forename: Saverio
authors.initials: S
authors.lastname: Minucci
authors.forename: Christian A G N
authors.initials: CA
authors.lastname: Montalbetti
authors.forename: Annett
authors.initials: A
authors.lastname: Müller
authors.forename: Deepti
authors.initials: D
authors.lastname: Patel
authors.forename: Banu G
authors.initials: BG
authors.lastname: Phillips
authors.forename: Mario
authors.initials: M
authors.lastname: Varasi
authors.forename: Mark
authors.initials: M
authors.lastname: Whittaker
authors.forename: Dirk
authors.initials: D
authors.lastname: Winkler
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Yarnold
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D018841:HSP90 Heat-Shock Proteins; D010091:Oximes; D011743:Pyrimidines