Identification of novel BRAF kinase inhibitors with structure-based virtual screening.

Authors: Park H, Choi H, Hong S, Hong S.
Publisher/Year: Bioorg Med Chem Lett. 2011 Oct 1;21(19):5753-6. Epub 2011 Aug 8.
Pub Med ID/Journal ID: PMID:21873050


VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has proved to be a promising target for the development of therapeutics for the treatment of a variety of human cancers. Here, we report the first example of a successful application of the structure-based virtual screening to identify novel BRAF inhibitors. These inhibitors have desirable physicochemical properties as a drug candidate, and compound 1 revealed a submicromolar binding affinity (0.7 µM). Therefore, they may serve as promising lead compounds for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of BRAF are discussed in detail. Copyright © 2011 Elsevier Ltd. All rights reserved.