title: A kinase-focused compound collection: compilation and screening strategy.
abstract: Lead identification by high-throughput screening of large compound libraries has been supplemented with virtual screening and focused compound libraries. To complement existing approaches for lead identification at Biogen Idec, a kinase-focused compound collection was designed, developed and validated. Two strategies were adopted to populate the compound collection: a ligand shape-based virtual screening and a receptor-based approach (structural interaction fingerprint). Compounds selected with the two approaches were cherry-picked from an existing high-throughput screening compound library, ordered from suppliers and supplemented with specific medicinal compounds from internal programs. Promising hits and leads have been generated from the kinase-focused compound collection against multiple kinase targets. The principle of the collection design and screening strategy was validated and the use of the kinase-focused compound collection for lead identification has been added to existing strategies.
authors.affiliation: Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. dongyu_sun@merck.com
authors.forename: Dongyu
authors.initials: D
authors.lastname: Sun
authors.forename: Claudio
authors.initials: C
authors.lastname: Chuaqui
authors.forename: Zhan
authors.initials: Z
authors.lastname: Deng
authors.forename: Scott
authors.initials: S
authors.lastname: Bowes
authors.forename: Donovan
authors.initials: D
authors.lastname: Chin
authors.forename: Juswinder
authors.initials: J
authors.lastname: Singh
authors.forename: Patrick
authors.initials: P
authors.lastname: Cullen
authors.forename: Gretchen
authors.initials: G
authors.lastname: Hankins
authors.forename: Wen-Cherng
authors.initials: WC
authors.lastname: Lee
authors.forename: Jason
authors.initials: J
authors.lastname: Donnelly
authors.forename: Jessica
authors.initials: J
authors.lastname: Friedman
authors.forename: Serene
authors.initials: S
authors.lastname: Josiah
mesh_terms: D020650:Combinatorial Chemistry Techniques; D030562:Databases, Protein; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010770:Phosphotransferases