8E5M

Structure of ARG1 complex with pyrrolidine-based non-boronic acid inhibitor 6

8E5M の概要

• エントリーDOI: 10.2210/pdb8e5m/pdb
• 分子名称: Arginase-1, MANGANESE (II) ION, 1-{[(3S,4S)-3-({4-[2-(4-fluorobenzene-1-sulfonyl)ethyl]piperidin-1-yl}methyl)-4-(3-fluorophenyl)pyrrolidin-1-yl]methyl}cyclopentane-1-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: arginase, hydrolase, urea cycle, metabolism, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 212786.86

構造登録者

Palte, R.L.,Gathiaka, S. (登録日: 2022-08-22, 公開日: 2023-03-08, 最終更新日: 2023-10-25)

主引用文献

Gathiaka, S.,Palte, R.L.,So, S.S.,Chai, X.,Richard Miller, J.,Kuvelkar, R.,Wen, X.,Cifelli, S.,Kreamer, A.,Liaw, A.,McLaren, D.G.,Fischer, C.
Discovery of non-boronic acid Arginase 1 inhibitors through virtual screening and biophysical methods.
Bioorg.Med.Chem.Lett., 84:129193-129193, 2023

PubMed Abstract: Inhibiting Arginase 1 (ARG1), a metalloenzyme that hydrolyzes l-arginine in the urea cycle, has been demonstrated as a promising therapeutic avenue in immuno-oncology through the restoration of suppressed immune response in several types of cancers. Most of the currently reported small molecule inhibitors are boronic acid based. Herein, we report the discovery of non-boronic acid ARG1 inhibitors through virtual screening. Biophysical and biochemical methods were used to experimentally profile the hits while X-ray crystallography confirmed a class of trisubstituted pyrrolidine derivatives as optimizable alternatives for the development of novel classes of immuno-oncology agents targeting this enzyme.

PubMed: 36822300
DOI: 10.1016/j.bmcl.2023.129193

実験手法

X-RAY DIFFRACTION (1.84 Å)