4A6L

beta-tryptase inhibitor

4A6L の概要

• エントリーDOI: 10.2210/pdb4a6l/pdb
• 関連するPDBエントリー: 1AAO
• 分子名称: TRYPTASE ALPHA/BETA-1, 1-{3-[1-({5-[(2-fluorophenyl)ethynyl]furan-2-yl}carbonyl)piperidin-4-yl]phenyl}methanamine (3 entities in total)
• 機能のキーワード: hydrolase, inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: Q15661
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 111575.55

構造登録者

Mathieu, M.,Maignan, S. (登録日: 2011-11-04, 公開日: 2012-01-25, 最終更新日: 2024-11-06)

主引用文献

Liang, G.,Aldous, S.,Merriman, G.,Levell, J.,Pribish, J.,Cairns, J.,Chen, X.,Maignan, S.,Mathieu, M.,Tsay, J.,Sides, K.,Rebello, S.,Whitely, B.,Morize, I.,Pauls, H.W.
Structure-Based Library Design and the Discovery of a Potent and Selective Mast Cell Beta-Tryptase Inhibitor as an Oral Therapeutic Agent.
Bioorg.Med.Chem.Lett., 22:1049-, 2012

PubMed Abstract: A solid phase combinatorial library was designed based on X-ray structures and in-silico models to explore an inducible S4+ pocket, which is formed by a simple side-chain rotation of Tyr95. This inducible S4+ pocket is unique to β-tryptase and does not exist for other trypsin-like serine proteases of interest. Therefore, inhibitors utilizing this pocket have inherent advantages for being selective against other proteases in the same family. A member of this library was found to be a potent and selective β-tryptase inhibitor with a suitable pharmacokinetic profile for further clinical evaluation.

PubMed: 22192588
DOI: 10.1016/J.BMCL.2011.11.119

実験手法

X-RAY DIFFRACTION (2.05 Å)