Pharmacophore and Binding Analysis of Known and Novel B-RAF Kinase Inhibitors

ISSN: 1875-533X (Online)
ISSN: 0929-8673 (Print)

Volume 24, 42 Issues, 2017

Download PDF Flyer

Current Medicinal Chemistry

This journal supports open access

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 10th of 59 in Chemistry & Medicinal
  • 63rd of 253 in Pharmacology & Pharmacy
  • 100th of 289 in Biochemistry & Molecular Biology

Submit Abstracts Online Submit Manuscripts Online

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 3.455
5 - Year: 3.792

Pharmacophore and Binding Analysis of Known and Novel B-RAF Kinase Inhibitors

Current Medicinal Chemistry, 21(17): 1938-1955.

Author(s): F. Baska, I. Szabadkai, A. Sipos, N. Breza, C. Szantai-Kis, L. Kekesi, R. Garamvolgyi, Z. Nemes, F. Baska, L. Neumann, R. Torka, A. Ullrich, G. Keri and L Orfi.

Affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes Endre utca 9. H-1092, Budapest, Hungary.


The extensively investigated serine/threonine kinase, B-RAF, is a member of the RAS/RAF/MEK/ERK pathway. It plays important role in the regulation of cell growth, differentiation and survival. The mutation of B-RAF occurs frequently in melanomas and colon tumors; therefore, it is considered as an outstanding therapeutic target. In recent years a great number of B-RAF inhibitors have been reported and this number is expected to increase. The aim of our work was to compare the structures and binding mode of the published B-RAF inhibitors, and then to apply the correlations found for the explanation of our experimental results. In the first part of this paper we describe the main pharmacophore features of the co-crysallized B-RAF inhibitors published in the literature, focusing on the binding modes and common structural elements. In the second part we present and characterize our recently developed B-RAF inhibitor family by application of in silico methods and in vitro kinetic profiling. The inhibitory activity of these compounds was determined in biochemical kinase- and cell-based assays. The docking and assay results support our conclusion that the presented compound family belongs to the type I 1/2subgroup, they inhibit B-RAF and B-RAF(V600E) mutant in a sub-micromolar range and most of them show selectivity towards B-RAF(V600E) mutant expressing cell lines with equal or even better IC50 values than sorafenib.


Binding mode, B-RAF, docking, kinase assay, kinase inhibitor, kinetic profiling.

Purchase Online Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 21
Issue Number: 17
First Page: 1938
Last Page: 1955
Page Count: 18
DOI: 10.2174/0929867321666140304152606
Price: $58

Related Journals

Webmaster Contact: Copyright © 2016 Bentham Science