Identification of FDA-Approved Small Molecules Capable of Disrupting the Calmodulin-Adenylyl Cyclase 8 Interaction through Direct Binding to Calmodulin.

ABSTRACT: Adenylyl cyclases (AC) catalyze the formation of cyclic AMP (cAMP) from ATP and are involved in a number of disease states, making them attractive potential drug targets. AC8, in particular, has been implicated in several neurological disorders. While development of small molecule AC inhibitors has generated some chemical leads, the lack of inhibitor specificity among AC family members has limited the identification of successful drug candidates. Therefore, finding alternative novel methods to suppress AC activity are needed. Because only AC1 and AC8 are robustly stimulated by calmodulin (CaM), we set out to explore the mechanism of disrupting the AC/CaM interaction as a way to selectively inhibit AC8. Through the development and implementation of a novel biochemical high-throughput-screen

SUBMITTER: Hayes MP 

PROVIDER: S-EPMC6362833 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature