Structure optimization of a new class of PPARγ antagonists.
Competitive PPARγ antagonist
MTTB
PPARγ
PPARγ agonist
PPARγ antagonist
SAR
SPPARγMs
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
13
05
2019
revised:
20
08
2019
accepted:
26
08
2019
pubmed:
25
9
2019
medline:
21
10
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
Peroxisome proliferator-activated receptor gamma (PPARγ) modulators have found wide application for the treatment of cancers, metabolic disorders and inflammatory diseases. Contrary to PPARγ agonists, PPARγ antagonists have been much less studied and although they have shown immunomodulatory effects, there is still no therapeutically useful PPARγ antagonist on the market. In contrast to non-competitive, irreversible inhibition caused by 2-chloro-5-nitrobenzanilide (GW9662), the recently described (E)-2-(5-((4-methoxy-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-(trifluoromethyl)benzyl)oxy)-benzylidene)-hexanoic acid (MTTB, T-10017) is a promising prototype for a new class of PPARγ antagonists. It exhibits competitive antagonism against rosiglitazone mediated activation of PPARγ ligand binding domain (PPARγLBD) in a transactivation assay in HEK293T cells with an IC
Identifiants
pubmed: 31548084
pii: S0968-0896(19)30780-1
doi: 10.1016/j.bmc.2019.115082
pii:
doi:
Substances chimiques
2-(5-((4-methoxy-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-(trifluoromethyl)benzyl)oxy)benzylidene)hexanoic acid
0
Cinnamates
0
PPAR gamma
0
Quinolines
0
Rosiglitazone
05V02F2KDG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115082Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.