Fragment-based identification of Hsp90 inhibitors.
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.
Barker
John J
JJ
Evotec, 114 Milton Park, Abingdon, Oxfordshire, OX10 4SA UK.
Barker
Oliver
O
Boggio
Roberto
R
Chauhan
Viddhata
V
Cheng
Robert K Y
RK
Corden
Vincent
V
Courtney
Stephen M
SM
Edwards
Neil
N
Falque
Virginie M
VM
Fusar
Fulvia
F
Gardiner
Mihaly
M
Hamelin
Estelle M N
EM
Hesterkamp
Thomas
T
Ichihara
Osamu
O
Jones
Richard S
RS
Mather
Owen
O
Mercurio
Ciro
C
Minucci
Saverio
S
Montalbetti
Christian A G N
CA
Müller
Annett
A
Patel
Deepti
D
Phillips
Banu G
BG
Varasi
Mario
M
Whittaker
Mark
M
Winkler
Dirk
D
Yarnold
Christopher J
CJ
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
D018841:HSP90 Heat-Shock Proteins; D010091:Oximes; D011743:Pyrimidines