Discovery and characterization of a small-molecule enteropeptidase inhibitor, SCO-792.
FRET
SCO‐792
covalent
enteropeptidase
Journal
Pharmacology research & perspectives
ISSN: 2052-1707
Titre abrégé: Pharmacol Res Perspect
Pays: United States
ID NLM: 101626369
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
07
02
2019
revised:
19
07
2019
accepted:
26
07
2019
entrez:
12
9
2019
pubmed:
12
9
2019
medline:
7
5
2020
Statut:
epublish
Résumé
Enteropeptidase, localized into the duodenum brush border, is a key enzyme catalyzing the conversion of pancreatic trypsinogen proenzyme to active trypsin, thereby regulating protein digestion and energy homeostasis. We report the discovery and pharmacological profiles of SCO-792, a novel inhibitor of enteropeptidase. A screen employing fluorescence resonance energy transfer was performed to identify enteropeptidase inhibitors. Inhibitory profiles were determined by in vitro assays. To evaluate the in vivo inhibitory effect on protein digestion, an oral protein challenge test was performed in rats. Our screen identified a series of enteropeptidase inhibitors, and compound optimization resulted in identification of SCO-792, which inhibited enteropeptidase activity in vitro, with IC
Identifiants
pubmed: 31508234
doi: 10.1002/prp2.517
pii: PRP2517
pmc: PMC6726858
doi:
Substances chimiques
Enzyme Inhibitors
0
Small Molecule Libraries
0
Enteropeptidase
EC 3.4.21.9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00517Déclaration de conflit d'intérêts
This study was conducted with the financial support of Takeda Pharmaceutical Company, Ltd. Among the authors, M.S., I.M., S.I., H.Y., H.H., K.T., K.H., Y.M., M.W., K.T., M.S., J.S., and T.K. are/were employees of Takeda Pharmaceutical Company Ltd., and Y.M. and M.W. are employees of SCOHIA PHARMA, Inc.
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