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

B. K. He; Z. Q. Ning; Z. B. Li; S. Shan; D. S. Pan; B. C. B. Ko; P. P. Li; Z. F. Shen; G. F. Dou; B. L. Zhang; X. P. Lu; Y. Gao

doi:10.1155/2012/546548

journal article Open Access Jan 01, 2012

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

B. K. He Z. Q. Ning Z. B. Li S. Shan D. S. Pan B. C. B. Ko P. P. Li Z. F. Shen G. F. Dou B. L. Zhang X. P. Lu Y. Gao

PPAR Research Vol. 2012 pp. 1-13 · Wiley

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Abstract

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 thein vitroandin vivodifferential effects of chiglitazar, a non-TZD type of PPAR pan-agonist currently in phase III clinic development in China, from PPARγ-selective agonist like rosiglitazone. Chiglitazar showed transactivating activity in each PPARα,γ, andδsubtype and upregulated the expression of PPARαand/or PPARδdownstream 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 indb/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. Thein vitroandin vivodifferential features of chiglitazar are informative and encouraging for the further development of this synthetic ligand for the potential use in T2DM.

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References

Details

Published: Jan 01, 2012
Vol/Issue: 2012
Pages: 1-13
License: View

Authors

B

B. K. He

Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Suite 2-601, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen 518057, China; Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China

Z

Z. Q. Ning

Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Suite 2-601, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen 518057, China

Z

Z. B. Li

Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Suite 2-601, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen 518057, China

S

S. Shan

Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Suite 2-601, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen 518057, China

D

D. S. Pan

Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Suite 2-601, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen 518057, China

B

B. C. B. Ko

Department of Chemistry, The University of Hong Kong, Hong Kong

P

P. P. Li

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

Z

Z. F. Shen

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

G

G. F. Dou

Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Transfusion Medicine, Beijing, China

B

B. L. Zhang

Tianjin University of Traditional Chinese Medicine, Tianjin, China

X

X. P. Lu

Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Suite 2-601, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen 518057, China

Y

Y. Gao

Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China

Cite This Article

B. K. He, Z. Q. Ning, Z. B. Li, et al. (2012). In VitroandIn VivoCharacterizations of Chiglitazar, a Newly Identified PPAR Pan-Agonist. PPAR Research, 2012, 1-13. https://doi.org/10.1155/2012/546548

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

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