4BB4

ephB4 kinase domain inhibitor complex

Summary for 4BB4

• Entry DOI: 10.2210/pdb4bb4/pdb
• Related: 2BBA 2VWU 2VWV 2VWW 2VWX 2VWY 2VWZ 2VX0 2VX1 2X9F 2XVD 4AW5
• Descriptor: EPHRIN TYPE-B RECEPTOR 4, N-(2-methoxyethyl)-4-[(6-pyridin-4-ylquinazolin-2-yl)amino]benzamide, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: transferase, unphosphorylated
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 34382.87

Authors

Read, J.,Brassington, C.A.,Green, I.,McCall, E.J.,Valentine, A.L. (deposition date: 2012-09-19, release date: 2013-02-27, Last modification date: 2024-05-08)

Primary citation

Vasbinder, M.M.,Aquila, B.,Augustin, M.,Chen, H.,Cheung, T.,Cook, D.,Drew, L.,Fauber, B.P.,Glossop, S.,Grondine, M.,Hennessy, E.J.,Johannes, J.,Lee, S.,Lyne, P.D.,Mortl, M.,Omer, C.,Palakurthi, S.,Pontz, T.,Read, J.,Sha, L.,Shen, M.,Steinbacher, S.,Wang, H.,Wu, A.,Ye, M.
Discovery and Optimization of a Novel Series of Potent Mutant B-Raf V600E Selective Kinase Inhibitors.
J.Med.Chem., 56:1996-, 2013

PubMed Abstract: B-Raf represents an attractive target for anticancer therapy and the development of small molecule B-Raf inhibitors has delivered new therapies for metastatic melanoma patients. We have discovered a novel class of small molecules that inhibit mutant B-Raf(V600E) kinase activity both in vitro and in vivo. Investigations into the structure-activity relationships of the series are presented along with efforts to improve upon the cellular potency, solubility, and pharmacokinetic profile. Compounds selectively inhibited B-Raf(V600E) in vitro and showed preferential antiproliferative activity in mutant B-Raf(V600E) cell lines and exhibited selectivity in a kinase panel against other kinases. Examples from this series inhibit growth of a B-Raf(V600E) A375 xenograft in vivo at a well-tolerated dose. In addition, aminoquinazolines described herein were shown to display pERK elevation in nonmutant B-Raf cell lines in vitro.

PubMed: 23398453
DOI: 10.1021/JM301658D

Experimental method

X-RAY DIFFRACTION (1.65 Å)