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

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Park H,Choi H,Hong S,Hong S

doi

10.1016/j.bmcl.2011.08.010

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

5753-6

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01081-X

journal_volume

21

pub_type

杂志文章

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