7R52

Crystal structure of human TLR8 in complex with Compound 2

7R52 の概要

• エントリーDOI: 10.2210/pdb7r52/pdb
• 分子名称: Toll-like receptor 8, 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, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: tlr8, toll-like receptor, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 192534.92

構造登録者

Faller, M.,Zink, F. (登録日: 2022-02-10, 公開日: 2022-03-23, 最終更新日: 2024-11-20)

主引用文献

Betschart, C.,Faller, M.,Zink, F.,Hemmig, R.,Blank, J.,Vangrevelinghe, E.,Bourrel, M.,Glatthar, R.,Behnke, D.,Barker, K.,Heizmann, A.,Angst, D.,Nimsgern, P.,Jacquier, S.,Junt, T.,Zipfel, G.,Ruzzante, G.,Loetscher, P.,Limonta, S.,Hawtin, S.,Andre, C.B.,Boulay, T.,Feifel, R.,Knoepfel, T.
Structure-Based Optimization of a Fragment-like TLR8 Binding Screening Hit to an In Vivo Efficacious TLR7/8 Antagonist.
Acs Med.Chem.Lett., 13:658-664, 2022

PubMed Abstract: Inappropriate activation of TLR7 and TLR8 is linked to several autoimmune diseases, such as lupus erythematosus. Here we report on the efficient structure-based optimization of the inhibition of TLR8, starting from a co-crystal structure of a small screening hit. Further optimization of the physicochemical properties for cellular potency and expansion of the structure-activity relationship for dual potency finally resulted in a highly potent TLR7/8 antagonist with demonstrated efficacy after oral dosing.

PubMed: 35450354
DOI: 10.1021/acsmedchemlett.1c00696

実験手法

X-RAY DIFFRACTION (2.943 Å)