The development and application of peroxisome proliferator-activated receptor (PPAR) modulator

doi:10.5246/jcps.2018.04.023

Abstract

Abstract:

The peroxisome proliferator-activated receptors (PPARs), PPARα, PPARβ/δ and PPARγ, are ligand-activated transcriptional factors, which belong to the nuclear receptor super family and play crucial roles in glucose and lipid metabolism. Based on the impressive advantages of PPAR agonists (like TZD and fibrate compounds) in the treatment of metabolic syndrome and type 2 diebetes, PPAR modulators have doubtlessly grabbed much more attention. However, serious clinical adverse effects, especially for PPARγ agonists, hinder the development of PPAR agonist. Therefore, the selectivity and safety would be the key points and have been taken into the consideration for novel generation PPAR agonist research, and then several dual- or pan-PPAR modulators have emerged. Furthermore, experimental study indicates that partial agonists can neutralize the side effect and achieve modest therapeutic effect. This review summaries structural features of PPAR receptors, illustrates the method of PPAR modulator design, then lists and analyzes recent dual- and pan- agonists.

Key words: PPAR receptors, Dual- modulator, Metabolic syndrome, T2D

CLC Number:

R916

Supporting:

Jian Xin, Xiangnan Xu, Yuping Wang, Zhentao Zhang, Yuheng Ma. The development and application of peroxisome proliferator-activated receptor (PPAR) modulator[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(4): 215-228.

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