5CT7

BRAF in Complex with RAF265

Summary for 5CT7

• Entry DOI: 10.2210/pdb5ct7/pdb
• Descriptor: Serine/threonine-protein kinase B-raf, 1-methyl-5-({2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl}oxy)-N-[4-(trifluoromethyl)phenyl]-1H-benzimidazol-2-amine (2 entities in total)
• Functional Keywords: kinase, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : P15056
• Total number of polymer chains: 2
• Total formula weight: 64864.59

Authors

Appleton, B.A. (deposition date: 2015-07-23, release date: 2015-09-09, Last modification date: 2024-03-06)

Primary citation

Williams, T.E.,Subramanian, S.,Verhagen, J.,McBride, C.M.,Costales, A.,Sung, L.,Antonios-McCrea, W.,McKenna, M.,Louie, A.K.,Ramurthy, S.,Levine, B.,Shafer, C.M.,Machajewski, T.,Renhowe, P.A.,Appleton, B.A.,Amiri, P.,Chou, J.,Stuart, D.,Aardalen, K.,Poon, D.
Discovery of RAF265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma.
Acs Med.Chem.Lett., 6:961-965, 2015

PubMed Abstract: Abrogation of errant signaling along the MAPK pathway through the inhibition of B-RAF kinase is a validated approach for the treatment of pathway-dependent cancers. We report the development of imidazo-benzimidazoles as potent B-RAF inhibitors. Robust in vivo efficacy coupled with correlating pharmacokinetic/pharmacodynamic (PKPD) and PD-efficacy relationships led to the identification of RAF265, 1, which has advanced into clinical trials.

PubMed: 26396681
DOI: 10.1021/ml500526p

Experimental method

X-RAY DIFFRACTION (3.17 Å)