3PRF

Crystal Structure of Human B-Raf Kinase Domain in Complex with a Non-Oxime Furopyridine Inhibitor

Summary for 3PRF

• Entry DOI: 10.2210/pdb3prf/pdb
• Related: 3PPJ 3PPK 3PRI
• Descriptor: Serine/threonine-protein kinase B-raf, 2-chloro-5-{[2-(pyrimidin-2-yl)furo[2,3-c]pyridin-3-yl]amino}phenol (2 entities in total)
• Functional Keywords: protein kinase, atp-competitive inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 71112.76

Authors

Voegtli, W.C.,Vigers, G.P.A.,Morales, T.,Brandhuber, B.J. (deposition date: 2010-11-29, release date: 2011-02-02, Last modification date: 2024-02-21)

Primary citation

Ren, L.,Wenglowsky, S.,Miknis, G.,Rast, B.,Buckmelter, A.J.,Ely, R.J.,Schlachter, S.,Laird, E.R.,Randolph, N.,Callejo, M.,Martinson, M.,Galbraith, S.,Brandhuber, B.J.,Vigers, G.,Morales, T.,Voegtli, W.C.,Lyssikatos, J.
Non-oxime inhibitors of B-Raf(V600E) kinase.
Bioorg.Med.Chem.Lett., 21:1243-1247, 2011

PubMed Abstract: The development of inhibitors of B-Raf(V600E) serine-threonine kinase is described. Various head-groups were examined to optimize inhibitor activity and ADME properties. Several of the head-groups explored, including naphthol, phenol and hydroxyamidine, possessed good activity but had poor pharmacokinetic exposure in mice. Exposure was improved by incorporating more metabolically stable groups such as indazole and tricyclic pyrazole, while indazole could also be optimized for good cellular activity.

PubMed: 21251822
DOI: 10.1016/j.bmcl.2010.12.061

Experimental method

X-RAY DIFFRACTION (2.9 Å)