4MBJ

Human B-Raf Kinase Domain in Complex with an Imidazopyridine-based Inhibitor

Summary for 4MBJ

• Entry DOI: 10.2210/pdb4mbj/pdb
• Descriptor: Serine/threonine-protein kinase B-raf, 2,6-difluoro-N-(1H-imidazo[4,5-b]pyridin-6-yl)-3-[(propylsulfonyl)amino]benzamide (2 entities in total)
• Functional Keywords: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (By similarity): P15056
• Total number of polymer chains: 2
• Total formula weight: 70409.04

Authors

Voegtli, W.C. (deposition date: 2013-08-19, release date: 2013-10-02, Last modification date: 2024-02-28)

Primary citation

Newhouse, B.J.,Wenglowsky, S.,Grina, J.,Laird, E.R.,Voegtli, W.C.,Ren, L.,Ahrendt, K.,Buckmelter, A.,Gloor, S.L.,Klopfenstein, N.,Rudolph, J.,Wen, Z.,Li, X.,Feng, B.
Imidazo[4,5-b]pyridine inhibitors of B-Raf kinase.
Bioorg.Med.Chem.Lett., 23:5896-5899, 2013

PubMed Abstract: This Letter details the synthesis and evaluation of imidazo[4,5-b]pyridines as inhibitors of B-Raf kinase. These compounds bind in a DFG-in, αC-helix out conformation of B-Raf, which is a binding mode associated with significant kinase selectivity. Structure-activity relationship studies involved optimization of the ATP-cleft binding region of these molecules, and led to compound 23, an inhibitor with excellent enzyme/cell potency, and kinase selectivity.

PubMed: 24042006
DOI: 10.1016/j.bmcl.2013.08.086

Experimental method

X-RAY DIFFRACTION (3.6 Å)