3NS7

Succinic Acid Amides as P2-P3 Replacements for Inhibitors of Interleukin-1beta Converting Enzyme (ICE or Caspase 1)

3NS7 の概要

• エントリーDOI: 10.2210/pdb3ns7/pdb
• 関連するBIRD辞書のPRD_ID: PRD_001011
• 分子名称: Caspase-1, (3S)-4-hydroxy-3-{[(2S)-4-{[2-(2-methyl-1H-benzimidazol-1-yl)ethyl]amino}-2-(1-methylethyl)-4-oxobutanoyl]amino}butanoic acid, ... (4 entities in total)
• 機能のキーワード: cysteine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P29466 P29466
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28975.34

構造登録者

Galatsis, P. (登録日: 2010-07-01, 公開日: 2011-08-17, 最終更新日: 2024-11-27)

主引用文献

Galatsis, P.,Caprathe, B.,Gilmore, J.,Thomas, A.,Linn, K.,Sheehan, S.,Harter, W.,Kostlan, C.,Lunney, E.,Stankovic, C.,Rubin, J.,Brady, K.,Allen, H.,Talanian, R.
Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1).
Bioorg.Med.Chem.Lett., 20:5184-5190, 2010

PubMed Abstract: Succinic acid amides have been found to be effective P2-P3 scaffold replacements for peptidic ICE inhibitors. Heteroarylalkyl fragments occupying the P4 position provided access to compounds with nM affinities. Utilization of an acylal prodrug moiety was required to overcome biopharmaceutical issues which led to the identification of 17f, a potential clinical candidate.

PubMed: 20656488
DOI: 10.1016/j.bmcl.2010.07.004

実験手法

X-RAY DIFFRACTION (2.6 Å)