6AGK

The structure of CH-II-77-tubulin complex

6AGK の概要

• エントリーDOI: 10.2210/pdb6agk/pdb
• 分子名称: Tubulin alpha-1B chain, [6-(3-hydroxy-4-methylphenyl)pyridin-2-yl](3,4,5-trimethoxyphenyl)methanone, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• 機能のキーワード: tubulin, complex, inhibitor, structural protein
• 由来する生物種: Sus scrofa (Pig); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 265165.36

構造登録者

Chen, H.,Arnst, K.,Wang, Y.,Miller, D.,Li, W. (登録日: 2018-08-13, 公開日: 2019-08-21, 最終更新日: 2023-11-22)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)