3ns7
From Proteopedia
Succinic Acid Amides as P2-P3 Replacements for Inhibitors of Interleukin-1beta Converting Enzyme (ICE or Caspase 1)
Structural highlights
FunctionCASP1_HUMAN Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.[1] [2] Publication Abstract from PubMedSuccinic 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. Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1).,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 Bioorg Med Chem Lett. 2010 Sep 1;20(17):5184-90. Epub 2010 Jul 8. PMID:20656488[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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