Structure-based design and in vivo anti-arthritic activity evaluation of a potent dipeptidyl cyclopropyl nitrile inhibitor of cathepsin C.
Cathepsin C
Cysteine protease
Inhibitor
Neutrophil
Serine protease
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
22
02
2019
accepted:
07
04
2019
pubmed:
13
4
2019
medline:
14
2
2020
entrez:
13
4
2019
Statut:
ppublish
Résumé
Cathepsin C (CatC) is a dipeptidyl-exopeptidase which activates neutrophil serine protease precursors (elastase, proteinase 3, cathepsin G and NSP4) by removing their N-terminal propeptide in bone marrow cells at the promyelocytic stage of neutrophil differentiation. The resulting active proteases are implicated in chronic inflammatory and autoimmune diseases. Hence, inhibition of CatC represents a therapeutic strategy to suppress excessive protease activities in various neutrophil mediated diseases. We designed and synthesized a series of dipeptidyl cyclopropyl nitrile compounds as putative CatC inhibitors. One compound, IcatC
Identifiants
pubmed: 30978322
pii: S0006-2952(19)30141-8
doi: 10.1016/j.bcp.2019.04.006
pii:
doi:
Substances chimiques
Anti-Asthmatic Agents
0
Cathepsin C
EC 3.4.14.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
349-367Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.