Title

Substrate activity screening with kinases: discovery of small-molecule substrate-competitive c-Src inhibitors

ACS Citation

Breen, M. E.; Steffey, M. E.; Lachacz, E. J.; Kwarcinski, F. E.; Fox, C. C.; Soellner, M. B. Substrate Activity Screening with Kinases: Discovery of Small‐Molecule Substrate‐Competitive c‐Src Inhibitors. Chem. Int. Ed., 2014, 53 7010-7013.

Abstract

Substrate-competitive kinase inhibitors represent a promising class of kinase inhibitors, however, there is no methodology to selectively identify this type of inhibitor. Substrate activity screening was applied to tyrosine kinases. By using this methodology, the first small-molecule substrates for any protein kinase were discovered, as well as the first substrate-competitive inhibitors of c-Src with activity in both biochemical and cellular assays. Characterization of the lead inhibitor demonstrates that substrate-competitive kinase inhibitors possess unique properties, including cellular efficacy that matches biochemical potency and synergy with ATP-competitive inhibitors.

Source Name

Angewandte Chemie

Publication Date

7-1-2014

Volume

53

Issue

27

Page(s)

7010-7013

Document Type

Citation

Citation Type

Article

Share

COinS