To accelerate the discovery of PPAR alpha/gamma dual agonists, the comparative molecular field analysis (CoMFA) were performed for PPAR alpha and PPAR gamma, respectively. Based on the molecular alignment, highly predictive CoMFA model for PPAR alpha was obtained with a cross-validated q(2) value...
Therefore, novel dual PPARα/γ agonists have received in- creasing attention given that they might enhance the sensi- tivity of target tissues to insulin via PPARγ activation and ©2006 CPS and SIMM 223 Xu C et al Acta Pharmacologica Sinica ISSN 1671-4083 improve lipid metabolic disorders ...
Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family Structure (2001) K.M. Darwish et al. Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARgamma/FFAR1 dual agonists Eur. J...
PPAR alpha/gamma dual agonists each target one or more of the key cardiometabolic risk factors of diabetic dyslipidemia, insulin resistance, hyperglycemia, and inflammation; thus, combining their benefits to provide glucose control and ameliorate cardiovascular risks has emerged as an attractive treatment...
molecular docking and ADME predictions were carried out using soft ware Schrodinger Suite 2009.Results: It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more ...
Synergistic effect of the human GLP-1 analogue liraglutide and a dual PPARα/γ agonist on glycaemic control in Zucker diabetic fatty rats uris J: Synergistic effect of the human GLP‑1 analogue liraglutide and a dual PPARalpha/gamma agonist on glycaemic control in Zucker diabetic fatty ... ...
Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and...
5-aryl thiazolidine-2,4-diones: discovery of PPAR dual alpha/gamma agonists as antidiabetic agents. Leung, K, Moller, DE, Heck, JV, Sahoo, SP (2003) 5-aryl thiazolidine-2,4-diones: discovery of PPAR Dual α/γ agonists as antidiabetic agents. ... R Desai,W Han,E Metzger,... -...
Fievet C, Fruchart JC, Staels B: PPARalpha and PPARgamma dual agonists for the treatment of type 2 diabetes and the metabolic syndrome. Current opinion in pharmacology. 2006, 6 (6): 606-614. 10.1016/j.coph.2006.06.009. Article CAS PubMed Google Scholar Easton DP, Kaneko Y, Subjeck...
A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compounds (S)-14 and (S)-19...