Ragaglitazar: a novel XXXX @entity9781 agonist with potent lipid-lowering and insulin-sensitizing efficacy in animal models.

@entity3725 @entity3724 @entity72944 @entity19 @entity409 @entity9781 @entity72943 @entity42665 @entity412 @entity35 @entity8151 @entity1720 @entity6170 @entity413 @entity165 @entity12891
Ragaglitazar [(-) @entity72943 ; NNC 61-0029] is a coligand of @entity3725 and @entity9781 . In ob/ob @entity19 , ragaglitazar showed significant reduction in plasma @entity413 , @entity412 and insulin (ED50 values <0.03, 6.1 and <0.1 mg kg-1). These effects are three-fold better than @entity6170 and @entity72944 . In Zucker fa/fa @entity35 , ragaglitazar showed dose-dependent reduction in @entity412 and insulin, hepatic @entity412 secretion and @entity412 clearance kinetics (maximum of 74, 53, 32 and 50% at 3 mg kg-1), which are better than @entity6170 and @entity72944 . In a high-fat-fed hyperlipidaemic @entity35 model, the compound showed an ED50 of 3.95, 3.78 mg kg-1 for @entity412 and @entity165 lowering, and 0.29 mg kg-1 for HDL-C increase. It also showed improvement in clearance of plasma @entity412 and hepatic @entity412 secretion rate. All these effects are 3-10-fold better than @entity3724 and @entity72944 . Ragaglitazar treatment showed significant reduction in plasma @entity8151 and @entity42665 levels, and increase in liver CPT1 and CAT activity and ACO mRNA. Significant @entity409 and fat LPL activity and fat @entity12891 mRNA was also observed. In a high-fat-fed hamster model, ragaglitazar at 1 mg kg-1 showed 83 and 61% reduction in @entity412 and total @entity165 , and also 17% reduction in fat feed-induced body weight increase. In these hyperlipidaemic animal models, @entity9781 ligands failed to show any significant efficacy. Taken together, ragaglitazar shows @entity1720 and lipid-lowering potential, as compared to the standard compounds.
