3NS7

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

Summary for 3NS7

Entry DOI	10.2210/pdb3ns7/pdb
Related PRD ID	PRD_001011
Descriptor	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)
Functional Keywords	cysteine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
Biological source	Homo sapiens (human) More
Cellular location	Cytoplasm: P29466 P29466
Total number of polymer chains	2
Total formula weight	28975.34
Authors	Galatsis, P. (deposition date: 2010-07-01, release date: 2011-08-17, Last modification date: 2024-11-27)
Primary citation	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 Cited by 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 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (2.6 Å)

Structure validation