In Vitroand In VivoCharacterizations of Chiglitazar, a Newly Identified PPAR Pan-Agonist

Solid rationales are still present for the identification of synthetic ligands to simultaneously target multiple PPAR subtypes for the treatment of T2DM. The purpose of this study was to characterize the in vitroand in vivodifferential effects of chiglitazar, a non-TZD type of PPAR pan-agonist curre...

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Bibliographic Details
Published in:PPAR research 2012-01, Vol.2012
Main Authors: He, B K, Ning, Z Q, Li, Z B, Shan, S, Pan, D S, Ko, B C B, Li, P P, Shen, Z F, Dou, G F, Zhang, B L, Lu, X P, Gao, Y
Format: Article
Language:English
Subjects:
Chemicals
Chinese medicine
Colleges & universities
Drug dosages
Fatty acids
Heart
Homeostasis
Insulin
Insulin resistance
Ligands
Metabolism
Proteins
Rodents
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Summary:Solid rationales are still present for the identification of synthetic ligands to simultaneously target multiple PPAR subtypes for the treatment of T2DM. The purpose of this study was to characterize the in vitroand in vivodifferential effects of chiglitazar, a non-TZD type of PPAR pan-agonist currently in phase III clinic development in China, from PPAR γ-selective agonist like rosiglitazone. Chiglitazar showed transactivating activity in each PPAR α, γ, and δsubtype and upregulated the expression of PPAR αand/or PPAR δdownstream genes involved in the key processes of lipid metabolism and thermogenesis. Comparable blood glucose lowering effect was observed between chiglitazar and rosiglitazone, but chiglitazar did not significantly increase the body weight in KKAy and fat pad weight in db/dbmice. Chiglitazar had high distribution in liver, pancreas, and skeleton muscles but was less present in kidney, heart, and adipose in rats. Heart weight increase was not observed in rats treated with chiglitazar for 6 months at a dose as high as 45 mg kg-1. The in vitroand in vivodifferential features of chiglitazar are informative and encouraging for the further development of this synthetic ligand for the potential use in T2DM.
ISSN:1687-4757
1687-4765
DOI:10.1155/2012/546548