Aleglitazar

Short Summary : PPARα/PPARγagonist

Category : Metabolism|PPAR

Purity : 0.98

CAS Number : 475479-34-6

Formula : C24H23NO5S

Molecular Weight : 437.51

SMILE : CC1=C(N=C(O1)C2=CC=CC=C2)CCOC3=C4C=CSC4=C(C=C3)CC(C(=O)O)OC

Solubility : Soluble in DMSO

Storage : Store at -20°C

Description : Aleglitazar is a potent dual agonist of peroxisome proliferator-activated receptor (PPAR) α/γ with IC50 values of 38 and 19 nM, respectively [1].PPAR are nuclear hormone receptors. They work as ligand-activated transcription factors and regulate gene expression with co-activators and co-repressors. PPARα usually takes participate in energy homeostasis while PPARγ plays critical roles in glucose homeostasis and insulin sensitivity. So far the agonists of PPAR α/γ are used in the treatment for dyslipidemia or typeII diabetes. Aleglitazar is a balanced and potent co-agonist of both PPARα and PPARγ based on α-alkoxyacid therefore is thought to be a probable opportunity to treat hyperglycemia and diabetes [1]. Aleglitazar showed similar affinities for both PPARα and PPARγ with IC50 values of 38 and 19 nM respectively in the radioligand binding assays. In the transcriptional assays using luciferase transcriptional reporter gene, aleglitazar showed EC50 values of 50 and 21 nM for PPARα and PPARγ, respectively. Aleglitazar had lower maximum activity towards PPARαthan other agonists suggesting that it was a partial PPARαagonist [1 and 2].In the primate model using rhesus monkeys, the oral administration of aleglitazar at dose of 0.03 mg/kg per day for 42 days resulted in significantly increased glucose disposal rate (7.8 to 12.5 mg/kg fat-free mass) and decreased TG levels (328 to 36 mg/dL). The FPG levels were reduced by aleglitazarfrom 89 to 75 mg/dL. Aleglitazar increased the levels of HDL-C by 125% and reduced LDL-C by 41%. Besides that, aleglitazar treatment increased the levels of ApoA-I and ApoA-II. In the euglycemic clamp study using Zuckerfa/farats, aleglitazar behaved more effectively than rosiglitazone and farglitazar [1 and 3]. References:[1] Bénardeau A, Benz J, Binggeli A, Blum D, Boehringer M, Grether U, Hilpert H, Kuhn B, Märki HP, Meyer M, Püntener K, Raab S, Ruf A, Schlatter D, Mohr P. Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. Bioorg Med Chem Lett. 2009 May 1;19(9):2468-73. doi: 10.1016/j.bmcl.2009.03.036..[2] Dietz M, Mohr P, Kuhn B, Maerki HP, Hartman P, Ruf A, Benz J, Grether U, Wright MB. Comparative molecular profiling of the PPARα/γ activator aleglitazar: PPAR selectivity, activity and interaction with cofactors. ChemMedChem. 2012 Jun;7(6):1101-11. [3] Hansen BC, Tigno XT, Bénardeau A, Meyer M, Sebokova E, Mizrahi J. Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor α/γ agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome. Cardiovasc Diabetol. 2011 Jan 20;10:7.

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