6YYN

Structure of Cathepsin S in complex with Compound 14

これはPDB形式変換不可エントリーです。

6YYN の概要

• エントリーDOI: 10.2210/pdb6yyn/pdb
• 分子名称: Cathepsin S, CITRATE ANION, ~{N}-methyl-3-[4-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperazin-1-yl]sulfonyl-propanamide, ... (5 entities in total)
• 機能のキーワード: cathepsin s, inhibitor, hydrolase
• 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: 51873.72

構造登録者

Wagener, M.,Schade, M.,Merla, B.,Hars, U.,Kueckelhaus, S.Q. (登録日: 2020-05-05, 公開日: 2021-05-12, 最終更新日: 2024-11-13)

主引用文献

Schade, M.,Merla, B.,Lesch, B.,Wagener, M.,Timmermanns, S.,Pletinckx, K.,Hertrampf, T.
Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors.
J.Med.Chem., 63:11801-11808, 2020

PubMed Abstract: Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.

PubMed: 32880457
DOI: 10.1021/acs.jmedchem.0c00949

実験手法

X-RAY DIFFRACTION (2.22 Å)