Design, synthesis and biological evaluation of indane derived GPR40 agoPAMs.
Diabetes
FFA1
GPCR
GPR40 AgoPAM
Indane
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 07 2019
15 07 2019
Historique:
received:
22
02
2019
revised:
16
04
2019
accepted:
30
04
2019
pubmed:
22
5
2019
medline:
10
9
2020
entrez:
22
5
2019
Statut:
ppublish
Résumé
GPR40 (FFAR1 or FFA1) is a G protein-coupled receptor, primarily expressed in pancreatic islet β-cells and intestinal enteroendocrine cells. When activated by fatty acids, GPR40 elicits increased insulin secretion from islet β-cells only in the presence of elevated glucose levels. Towards this end, studies were undertaken towards discovering a novel GPR40 Agonist whose mode of action is via Positive Allosteric Modulation of the GPR40 receptor (AgoPAM). Efforts were made to identify a suitable GPR40 AgoPAM tool molecule to investigate mechanism of action and de-risk liver toxicity of GPR40 AgoPAMs due to reactive acyl-glucuronide (AG) metabolites.
Identifiants
pubmed: 31109791
pii: S0960-894X(19)30283-5
doi: 10.1016/j.bmcl.2019.04.050
pii:
doi:
Substances chimiques
Indans
0
Receptors, G-Protein-Coupled
0
indan
H9SCX043IG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1842-1848Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.