Anti-diabetic activity of fused PPAR ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
Title :
Anti-diabetic activity of fused PPAR gamma-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression
Author(s) :
Pirat, Celine [Auteur]
Dacquet, Catherine [Auteur]
Leclerc, Veronique [Auteur]
Hennuyer, Nathalie [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Beucher-Gaudin, Monique [Auteur]
Zanirato, Ghislaine [Auteur]
Geant, Anne [Auteur]
Staels, Bart [Auteur]
Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Ktorza, Alain [Auteur]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Caignard, Daniel-Henri [Auteur]
Berthelot, Pascal [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Lebegue, Nicolas [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Dacquet, Catherine [Auteur]
Leclerc, Veronique [Auteur]
Hennuyer, Nathalie [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Beucher-Gaudin, Monique [Auteur]
Zanirato, Ghislaine [Auteur]
Geant, Anne [Auteur]
Staels, Bart [Auteur]
Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Ktorza, Alain [Auteur]
Farce, Amaury [Auteur]

Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Caignard, Daniel-Henri [Auteur]
Berthelot, Pascal [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Lebegue, Nicolas [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Journal title :
European journal of medicinal chemistry
Abbreviated title :
Eur. J. Med. Chem.
Volume number :
137
Pages :
310-326
Publication date :
2017-09-08
ISSN :
0223-5234
English keyword(s) :
SGK1
SIRT1
PPAR
Diabetes
Resveratrol
Calorie restriction
Body-weight gain
SIRT1
PPAR
Diabetes
Resveratrol
Calorie restriction
Body-weight gain
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the ...
Show more >A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPARγ agonist activity (Emax = 98%, EC = 200 nM), SIRT1 enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGK1 expression.Show less >
Show more >A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPARγ agonist activity (Emax = 98%, EC = 200 nM), SIRT1 enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGK1 expression.Show less >
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Institut Pasteur de Lille
Inserm
Université de Lille
Institut Pasteur de Lille
Collections :
Research team(s) :
Therapeutic innovation targetting inflammation
Submission date :
2019-05-17T13:14:42Z
2021-06-10T16:12:24Z
2021-06-10T16:12:24Z