7MFH

Crystal structure of BIO-32546 bound mouse Autotaxin

7MFH の概要

• エントリーDOI: 10.2210/pdb7mfh/pdb
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: hydrolase inhibitor, autotaxin, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 99445.25

構造登録者

Chodaparambil, J.V. (登録日: 2021-04-09, 公開日: 2022-04-13, 最終更新日: 2024-11-20)

主引用文献

Ma, B.,Zhang, L.,Sun, L.,Xin, Z.,Kumaravel, G.,Marcotte, D.,Chodaparambil, J.V.,Wang, Q.,Wehr, A.,Jing, J.,Hong, V.S.,Wang, T.,Huang, C.,Shao, Z.,Mi, S.
Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546.
Acs Med.Chem.Lett., 12:1124-1129, 2021

PubMed Abstract: Autotaxin (ATX) is a lysophospholipase D that is the main enzyme responsible for generating LPA in body fluids. Although ATX was isolated from a conditioned medium of melanoma cells, later it was discovered to play a critical role in vascular and neuronal development. ATX has also been implicated in primary brain tumor, fibrosis, and rheumatoid arthritis, as well as neurological diseases such as multiple sclerosis, Alzheimer's disease, and neuropathic pain. As ATX and LPA levels are increased upon neuronal injury, a selective ATX inhibitor could provide a new approach to treat neuropathic pain. Herein we describe the discovery of a novel series of nonzinc binding reversible ATX inhibitors, particularly a potent, selective, orally bioavailable, brain-penetrable tool compound BIO-32546, as well as its synthesis, X-ray cocrystal structure, pharmacokinetics, and in vivo efficacy.

PubMed: 34267882
DOI: 10.1021/acsmedchemlett.1c00211

実験手法

X-RAY DIFFRACTION (2.3 Å)