Extending kinome coverage by analysis of kinase inhibitor broad profiling data.

Autor: Jacoby E; Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: ejacoby@its.jnj.com., Tresadern G; Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Bembenek S; Janssen Research & Development, La Jolla, 3210 Merryfield Row, San Diego, CA 92121, USA., Wroblowski B; Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Buyck C; Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Neefs JM; Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Rassokhin D; Janssen Research & Development, Spring House, 1400 McKean Road, Spring House, PA 19002, USA., Poncelet A; Janssen Research & Development, Val de Reuil, Campus de Maigremont, B.P. 615, 27106 Val De Reuil Cedex, France., Hunt J; KINOMEscan Division of DiscoveRx Corporation, 11180 Roselle Street, Suite D, San Diego, CA 92121, USA., van Vlijmen H; Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: hvvlijme@its.jnj.com.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2015 Jun; Vol. 20 (6), pp. 652-8. Date of Electronic Publication: 2015 Jan 14.
DOI: 10.1016/j.drudis.2015.01.002
Abstrakt: The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors on 456 kinases in the DiscoveRx format delivered several insights. First, the coverage depended on the threshold of the selectivity parameter. Second, the relation between hit confirmation rates and inhibitor selectivity showed unexpectedly that higher selectivity can increase the likelihood of false positives. Third, comparing the coverage of a focused to that of a random library showed that the design based on a maximum number of scaffolds was superior to a limited number of scaffolds. Therefore, selective compounds can be used in target validation, enable the jumpstarting of new kinase drug discovery projects, and chart new biological space via phenotypic screening.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: