Highly Selective Inhibitors of Dipeptidyl Peptidase 9 (DPP9) Derived from the Clinically Used DPP4-Inhibitor Vildagliptin.

Dipeptidyl Peptidase 4 Dipeptidyl-Peptidase IV Inhibitors / pharmacology Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors Proline Protease Inhibitors Serine Endopeptidases Vildagliptin / pharmacology

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
28 09 2023
Historique:
medline: 23 10 2023
pubmed: 18 9 2023
entrez: 18 9 2023
Statut: ppublish

Résumé

Dipeptidyl peptidase 9 (DPP9) is a proline-selective serine protease that plays a key role in NLRP1- and CARD8-mediated inflammatory cell death (pyroptosis). No selective inhibitors have hitherto been reported for the enzyme: all published molecules have grossly comparable affinities for DPP8 and 9 because of the highly similar architecture of these enzymes' active sites. Selective DPP9 inhibitors would be highly instrumental to address unanswered research questions on the enzyme's role in pyroptosis, and they could also be investigated as therapeutics for acute myeloid leukemias. Compounds presented in this manuscript (

Identifiants

DOI: 10.1021/acs.jmedchem.3c00609 PMID: 37721854
pubmed: 37721854
doi: 10.1021/acs.jmedchem.3c00609
doi:

Substances chimiques

Dipeptidyl Peptidase 4 EC 3.4.14.5
Dipeptidyl-Peptidase IV Inhibitors 0
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases EC 3.4.14.-
Proline 9DLQ4CIU6V
Protease Inhibitors 0
Serine Endopeptidases EC 3.4.21.-
Vildagliptin I6B4B2U96P
DPP9 protein, human EC 3.4.14.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12717-12738

Auteurs

Siham Benramdane (S)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Joni De Loose (J)

Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Nicolò Filippi (N)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Margarida Espadinha (M)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Olivier Beyens (O)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Yentl Van Rymenant (YV)

Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Laura Dirkx (L)

Laboratory of Microbiology, Parasitology and Hygiene, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Murat Bozdag (M)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Pim-Bart Feijens (PB)

Laboratory of Microbiology, Parasitology and Hygiene, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Koen Augustyns (K)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
ORCID: 0000-0002-5203-4339

Guy Caljon (G)

Laboratory of Microbiology, Parasitology and Hygiene, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Hans De Winter (H)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
ORCID: 0000-0002-4450-7677

Ingrid De Meester (I)

Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Pieter Van der Veken (P)

Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
ORCID: 0000-0003-1208-3571

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Dipeptidyl peptidase 4 › Highly Selective Inhibitors of Dipeptidyl...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Inhibiteurs de la dipeptidyl-peptidase IV › Highly Selective Inhibitors of Dipeptidyl...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Exopeptidases › Dipeptidyl-Peptidases and Tripeptidyl-Peptidases › Highly Selective Inhibitors of Dipeptidyl...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés cycliques › Imino-acides › Proline › Highly Selective Inhibitors of Dipeptidyl...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéases › Highly Selective Inhibitors of Dipeptidyl...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Highly Selective Inhibitors of Dipeptidyl...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrrolidines › Vildagliptine › Highly Selective Inhibitors of Dipeptidyl...