2ZEC

Potent, Nonpeptide Inhibitors of Human Mast Cell Tryptase

2ZEC の概要

• エントリーDOI: 10.2210/pdb2zec/pdb
• 関連するPDBエントリー: 2ZEB
• 分子名称: Tryptase beta 2, 1-[1'-(3-phenylacryloyl)spiro[1-benzofuran-3,4'-piperidin]-5-yl]methanamine (3 entities in total)
• 機能のキーワード: tryptase, serine protease, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 110454.28

構造登録者

Spurlino, J.C.,Lewandowski, F.,Milligan, C. (登録日: 2007-12-08, 公開日: 2008-12-09, 最終更新日: 2024-10-30)

主引用文献

Costanzo, M.J.,Yabut, S.C.,Zhang, H.-C.,White, K.B.,de Garavilla, L.,Wang, Y.,Minor, L.K.,Tounge, B.A.,Barnakov, A.N.,Lewandowski, F.,Milligan, C.,Spurlino, J.C.,Abraham, W.M.,Boswell-Smith, V.,Page, C.P.,Maryanoff, B.E.
Potent, nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives
Bioorg.Med.Chem.Lett., 18:2114-2121, 2008

PubMed Abstract: We have explored a series of spirocyclic piperidine amide derivatives (5) as tryptase inhibitors. Thus, 4 (JNJ-27390467) was identified as a potent, selective tryptase inhibitor with oral efficacy in two animal models of airway inflammation (sheep and guinea pig asthma models). An X-ray co-crystal structure of 4 x tryptase revealed a hydrophobic pocket in the enzyme's active site, which is induced by the phenylethynyl group and is comprised of amino acid residues from two different monomers of the tetrameric protein.

PubMed: 18272363
DOI: 10.1016/j.bmcl.2008.01.093

実験手法

X-RAY DIFFRACTION (2.059 Å)