6PC4

Tubulin-RB3_SLD-TTL in complex with compound ABI-274

Summary for 6PC4

• Entry DOI: 10.2210/pdb6pc4/pdb
• Related: 6AGK
• Descriptor: Tubulin alpha-1B chain, [2-(4-methylphenyl)-1H-imidazol-4-yl](3,4,5-trimethoxyphenyl)methanone, Tubulin beta-2B chain, ... (11 entities in total)
• Functional Keywords: microtubule inhibitor, colchicine, cancer, cell cycle
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 264486.05

Authors

Kumar, G.,Wang, Y.,Li, W.,White, S.W. (deposition date: 2019-06-15, release date: 2020-04-22, Last modification date: 2024-03-13)

Primary citation

Chen, H.,Deng, S.,Wang, Y.,Albadari, N.,Kumar, G.,Ma, D.,Li, W.,White, S.W.,Miller, D.D.,Li, W.
Structure-Activity Relationship Study of Novel 6-Aryl-2-benzoyl-pyridines as Tubulin Polymerization Inhibitors with Potent Antiproliferative Properties.
J.Med.Chem., 63:827-846, 2020

PubMed Abstract: We recently reported the crystal structure of tubulin in complex with a colchicine binding site inhibitor (CBSI), ABI-231, having 2-aryl-4-benzoyl-imidazole (ABI). Based on this and additional crystal structures, here we report the structure-activity relationship study of a novel series of pyridine analogues of ABI-231, with compound being the most potent one (average IC ∼ 1.8 nM) against a panel of cancer cell lines. We determined the crystal structures of another potent CBSI ABI-274 and in complex with tubulin and confirmed their direct binding at the colchicine site. inhibited tubulin polymerization, strongly suppressed A375 melanoma tumor growth, induced tumor necrosis, disrupted tumor angiogenesis, and led to tumor cell apoptosis in vivo. Collectively, these studies suggest that represents a promising new generation of tubulin inhibitors.

PubMed: 31860298
DOI: 10.1021/acs.jmedchem.9b01815

Experimental method

X-RAY DIFFRACTION (2.602 Å)