Bivalent Inhibitors of c-Src Tyrosine Kinase That Bind a Regulatory Domain.

ABSTRACT: We have developed a general methodology to produce bivalent kinase inhibitors for c-Src that interact with the SH2 and ATP binding pockets. Our approach led to a highly selective bivalent inhibitor of c-Src. We demonstrate impressive selectivity for c-Src over homologous kinases. Exploration of the unexpected high level of selectivity yielded insight into the inherent flexibility of homologous kinases. Finally, we demonstrate that our methodology is modular and both the ATP-competitive fragment and conjugation chemistry can be swapped.

SUBMITTER: Johnson TK 

PROVIDER: S-EPMC7238493 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature