Testing the promiscuity of commercial kinase inhibitors against the AGC kinase group using a split-luciferase screen

Benjamin W. Jester, Alicia Gaj, Carolyn D. Shomin, Kurt J. Cox, Indraneel Ghosh

Research output: Contribution to journalArticle

19 Scopus citations


Using a newly developed competitive binding assay dependent upon the reassembly of a split reporter protein, we have tested the promiscuity of a panel of reported kinase inhibitors against the AGC group. Many non-AGC targeted kinase inhibitors target multiple members of the AGC group. In general, structurally similar inhibitors consistently exhibited activity toward the same target as well as toward closely related kinases. The inhibition data was analyzed to test the predictive value of either using identity scores derived from residues within 6 Å of the active site or identity scores derived from the entire kinase domain. The results suggest that the active site identity in certain cases may be a stronger predictor of inhibitor promiscuity. The overall results provide general guidelines for establishing inhibitor selectivity as well as for the future design of inhibitors that either target or avoid AGC kinases.

Original languageEnglish (US)
Pages (from-to)1526-1537
Number of pages12
JournalJournal of Medicinal Chemistry
Issue number4
Publication statusPublished - Feb 23 2012


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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