Identification of "latent hits" in compound screening collections.
The relatively low hit rates found from high-throughput screening have raised a question on whether this technology alone is sufficient to maximally exploit the full potential of current corporate screening collections. The present study introduces a knowledge-based strategy for identifying "latent hits", i.e., inactive compounds that could potentially be promoted to hits through simple chemical transformations. Examples are given of submicromolar agonist hits derived from the corresponding latent hits for the estrogen receptor.
Mestres
Jordi
J
Computational Medicinal Chemistry, Organon Laboratories Ltd., Newhouse ML1 5SH, Scotland, U.K. j.mestres@organon.co.uk
Veeneman
Gerrit H
GH
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D051381:Rats; D011960:Receptors, Estrogen / Q000819:agonists*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
D047628:Estrogen Receptor alpha; D008024:Ligands; D011960:Receptors, Estrogen; D004958:Estradiol