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. Author manuscript; available in PMC: 2011 Apr 1.
Published in final edited form as: Cancer Res. 2010 Aug 31;70(20):8036–8044. doi: 10.1158/0008-5472.CAN-10-1366

Figure 1. Compound 1t is a potent and selective inhibitor of oncogenic BRAF.

Figure 1

(A) Chemical structure of 1t/CCT239065 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(2-(methylthio)-4-(3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)phenyl)urea (B) Inhibition of recombinant full-length V600EBRAF in vitro by 1t (○) and inhibition of ERK (measured by activation segment phosphorylation) in WM266.4 (V600DBRAF) melanoma cells following a 6 h exposure to increasing concentrations of 1t (●). (C) Selectivity profile of 1 μM 1t tested against a panel of 80 kinases (inset). Kinases inhibited by >70% are presented in the main histogram. (D) Docking of 1t into the co-crystal structure of BRAF and sorafenib (pdb code UWH). The BPI pocket formed by residues Val471, Ala481, Lys483 and Ile527 is indicated by the red surface.