4Z0L

The murine cyclooxygenase-2 complexed with a nido-dicarbaborate-containing indomethacin derivative

4Z0L の概要

• エントリーDOI: 10.2210/pdb4z0l/pdb
• 分子名称: Prostaglandin G/H synthase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, PROTOPORPHYRIN IX CONTAINING FE, ... (8 entities in total)
• 機能のキーワード: cyclooxygenase, indomethacin, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 279778.59

構造登録者

Xu, S.,Neumann, W.,Banerjee, S.,Hey-Hawkins, E.,Marnett, L.J. (登録日: 2015-03-26, 公開日: 2015-06-10, 最終更新日: 2024-11-13)

主引用文献

Neumann, W.,Xu, S.,Sarosi, M.B.,Scholz, M.S.,Crews, B.C.,Ghebreselasie, K.,Banerjee, S.,Marnett, L.J.,Hey-Hawkins, E.
nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2.
Chemmedchem, 11:175-178, 2016

PubMed Abstract: Carbaboranes are increasingly studied as pharmacophores, particularly as replacements for aromatic systems. However, especially ortho-carbaborane is prone to degradation of the cluster, which hampers biological application. This study demonstrates that deboronation of the cluster may not only lead to a more active analogue, but can also improve the solubility and stability of a carbaborane-containing inhibitor. Notably, introduction of a nido-dicarbaborate cluster into the cyclooxygenase (COX) inhibitor indomethacin results in remarkably increased inhibitory potency and selectivity for COX-2 relative to the respective phenyl analogue. The first crystal structure of a carbaborane-containing inhibitor bound to COX-2 further reveals a novel binding mode for the inhibitor that is strikingly different from that of indomethacin. These results indicate that nido-dicarbaborate is a promising pharmacophore that exhibits properties which are also highly beneficial for its introduction into other inhibitor classes.

PubMed: 26088701
DOI: 10.1002/cmdc.201500199

実験手法

X-RAY DIFFRACTION (2.29 Å)