A kinase-focused compound collection: compilation and screening strategy.
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.
Sun
Dongyu
D
Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. dongyu_sun@merck.com
Chuaqui
Claudio
C
Deng
Zhan
Z
Bowes
Scott
S
Chin
Donovan
D
Singh
Juswinder
J
Cullen
Patrick
P
Hankins
Gretchen
G
Lee
Wen-Cherng
WC
Donnelly
Jason
J
Friedman
Jessica
J
Josiah
Serene
S
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
D008024:Ligands; D010770:Phosphotransferases