Docking-based structural splicing and reassembly strategy to develop novel deazapurine derivatives as potent B-Raf^V600E inhibitors.

ABSTRACT: The mutation of B-Raf^V600E is widespread in a variety of human cancers. Its inhibitors vemurafenib and dabrafenib have been launched as drugs for treating unresectable melanoma, demonstrating that B-Raf^V600E is an ideal drug target. This study focused on developing novel B-Raf^V600E inhibitors as drug leads against various cancers with B-Raf^V600E mutation. Using molecular modeling approaches, 200 blockbuster drugs were spliced to generate 283 fragments followed by molecular docking to identify potent fragments. Molecular structures of potential inhibitors of B-Raf^V600E were then obtained by fragment reassembly followed by docking to predict the bioactivity of the reassembled molecules. The structures with high predicted bioactivity were

SUBMITTER: Wang GM 

PROVIDER: S-EPMC5519245 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature