5MZC

Pseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid

5MZC の概要

• エントリーDOI: 10.2210/pdb5mzc/pdb
• 分子名称: Kynurenine 3-monooxygenase, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: kmo, oxidoreductase
• 由来する生物種: Pseudomonas fluorescens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 104733.63

構造登録者

Rowland, P. (登録日: 2017-01-31, 公開日: 2017-04-19, 最終更新日: 2024-05-08)

主引用文献

Walker, A.L.,Ancellin, N.,Beaufils, B.,Bergeal, M.,Binnie, M.,Bouillot, A.,Clapham, D.,Denis, A.,Haslam, C.P.,Holmes, D.S.,Hutchinson, J.P.,Liddle, J.,McBride, A.,Mirguet, O.,Mowat, C.G.,Rowland, P.,Tiberghien, N.,Trottet, L.,Uings, I.,Webster, S.P.,Zheng, X.,Mole, D.J.
Development of a Series of Kynurenine 3-Monooxygenase Inhibitors Leading to a Clinical Candidate for the Treatment of Acute Pancreatitis.
J. Med. Chem., 60:3383-3404, 2017

PubMed Abstract: Recently, we reported a novel role for KMO in the pathogenesis of acute pancreatitis (AP). A number of inhibitors of kynurenine 3-monooxygenase (KMO) have previously been described as potential treatments for neurodegenerative conditions and particularly for Huntington's disease. However, the inhibitors reported to date have insufficient aqueous solubility relative to their cellular potency to be compatible with the intravenous (iv) dosing route required in AP. We have identified and optimized a novel series of high affinity KMO inhibitors with favorable physicochemical properties. The leading example is exquisitely selective, has low clearance in two species, prevents lung and kidney damage in a rat model of acute pancreatitis, and is progressing into preclinical development.

PubMed: 28398044
DOI: 10.1021/acs.jmedchem.7b00055

実験手法

X-RAY DIFFRACTION (1.82 Å)