3II5

The Complex of wild-type B-RAF with Pyrazolo pyrimidine inhibitor

Summary for 3II5

• Entry DOI: 10.2210/pdb3ii5/pdb
• Related: 1UWH
• Descriptor: B-Raf proto-oncogene serine/threonine-protein kinase, N-[3-(3-{4-[(dimethylamino)methyl]phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-3-(trifluoromethyl)benzamide, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: b-raf, kinase, protein-inhibitor complex, acetylation, atp-binding, cardiomyopathy, cytoplasm, disease mutation, metal-binding, nucleotide-binding, phorbol-ester binding, phosphoprotein, polymorphism, proto-oncogene, serine/threonine-protein kinase, transferase, zinc, zinc-finger
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (By similarity): P15056
• Total number of polymer chains: 2
• Total formula weight: 71542.16

Authors

Xu, W.,Breger, D.,Torres, N.,Dutia, M.,Powell, D.,Ciszewski, G. (deposition date: 2009-07-31, release date: 2009-11-10, Last modification date: 2024-02-21)

Primary citation

Berger, D.M.,Torres, N.,Dutia, M.,Powell, D.,Ciszewski, G.,Gopalsamy, A.,Levin, J.I.,Kim, K.H.,Xu, W.,Wilhelm, J.,Hu, Y.,Collins, K.,Feldberg, L.,Kim, S.,Frommer, E.,Wojciechowicz, D.,Mallon, R.
Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors.
Bioorg.Med.Chem.Lett., 19:6519-6523, 2009

PubMed Abstract: As part of our research effort to discover B-Raf kinase inhibitors, we prepared a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides. X-ray crystallography studies revealed that one of the more potent inhibitors (10n) bound to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.

PubMed: 19864136
DOI: 10.1016/j.bmcl.2009.10.049

Experimental method

X-RAY DIFFRACTION (2.79 Å)