Discovery of Mcl-1 inhibitors from integrated high throughput and virtual screening.

ABSTRACT: Protein-protein interactions (PPIs) represent important and promising therapeutic targets that are associated with the regulation of various molecular pathways, particularly in cancer. Although they were once considered "undruggable," the recent advances in screening strategies, structure-based design, and elucidating the nature of hot spots on PPI interfaces, have led to the discovery and development of successful small-molecule inhibitors. In this report, we are describing an integrated high-throughput and computational screening approach to enable the discovery of small-molecule PPI inhibitors of the anti-apoptotic protein, Mcl-1. Applying this strategy, followed by biochemical, biophysical, and biological characterization, nineteen new chemical scaffolds were discovered and validated a

SUBMITTER: Mady ASA 

PROVIDER: S-EPMC6033896 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature