Identification of BRAF inhibitors through in silico screening.

ABSTRACT: The BRAF protein kinase, a molecule in the RAS-RAF-MEK-ERK signaling pathway, is mutated to harbor elevated kinase activity in approximately 7% of human cancers, which makes it an important therapeutic target for inhibition. Several BRAF protein-kinase inhibitors have been developed through high-throughout screening in vitro; however, many of these compounds suffer from a lack of suitable kinase specificity and other chemotherapeutic properties. In silico screening has evolved as a powerful complimentary approach to protein-kinase inhibitor identification. Here we describe an in silico screen for BRAF inhibitors that leads to the identification of a series of purine-2,6-dione analogues with IC50 values in the single-digit micromolar range and with significant selectivity for BRAF over othe

SUBMITTER: Luo C 

PROVIDER: S-EPMC4010122 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature