Discovery of novel low molecular weight inhibitors of IMPDH via virtual needle screening.
Novel, low molecular weight inhibitors of IMPDH have been discovered through the application of a validated virtual screening protocol. A series of 21 IMPDH inhibitors were used to validate the docking procedure. Application of this procedure to the selection of compounds for screening from an in-house database resulted in a 50-fold reduction in the size of the screening set (3425 to 74 compounds) and gave a hit-rate of 10% on biological evaluation.
Pickett
Stephen D
SD
Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, Herts AL7 3AY, UK. stephen.d.pickett@gsk.com
Sherborne
Bradley S
BS
Wilkinson
Trevor
T
Bennett
James
J
Borkakoti
Neera
N
Broadhurst
Michael
M
Hurst
David
D
Kilford
Ian
I
McKinnell
Murray
M
Jones
Philip S
PS
D001665:Binding Sites; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008970:Molecular Weight; D013329:Structure-Activity Relationship; D014867:Water
D004791:Enzyme Inhibitors; D014867:Water; D007168:IMP Dehydrogenase