Allosteric Tuning of Caspase-7: A Fragment-Based Drug Discovery Approach.

ABSTRACT: The caspase family of cysteine proteases are highly sought-after drug targets owing to their essential roles in apoptosis, proliferation, and inflammation pathways. High-throughput screening efforts to discover inhibitors have gained little traction. Fragment-based screening has emerged as a powerful approach for the discovery of innovative drug leads. This method has become a central facet of drug discovery campaigns in the pharmaceutical industry and academia. A fragment-based drug discovery campaign against human caspase-7 resulted in the discovery of a novel series of allosteric inhibitors. An X-ray crystal structure of caspase-7 bound to a fragment hit and a thorough kinetic characterization of a zymogenic form of the enzyme were used to investigate the allosteric mechanism of inhibit

SUBMITTER: Vance NR 

PROVIDER: S-EPMC5698726 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature