Multitargeted bioactive ligands for PPARs discovered in the last decade.
Type 2 diabetes took insulin resistance as the main clinical manifestation. PPARs have been reported to be the therapeutic targets of metabolic disorders, such as obesity, hypertension, diabetes, and cardiovascular disease. Previously, PPARγ agonist rosiglitazone was restricted in clinic due to cardiomyocytes infarction, weight gain, and other serious side-effects, which were mainly due to the single and selective PPARγ agonism. In recent years, multitarget-directed PPAR agonists with synergistic reaction as well as fewer side-effect have been the hot topic in designing promising agents. In this review, we updated and generalized the development of PPARγ partial agonists, PPARγ antagonists, PPARα/γ dual agonists, PPARδ partial agonists, PPARδ antagonists, PPARα/δ dual agonists, PPARγ/δ dual agonists, and PPARα/γ/δ pan-agonists published in recent decade. Most of these molecules were modified from known structures or came from high-throughput screening. Among these molecules, some were expected to be promising drugs against metabolic disorders, while others seemed to provide new insight for designing novel PPAR agents.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
Jun
J
Zhang
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
Xin
X
Liu
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
Xian-Bin
XB
Xie
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China. chengxianchao@aliyun.com.
Xian-Chao
XC
Cheng
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
Run-Ling
RL
Wang
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D008024:Ligands; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
C000592277:7-(2-(2-(2-cyclopentylvinyl)-5-methyloxazol-4-yl)-ethoxy)-2-(2,4-hexadienoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; D007004:Hypoglycemic Agents; D007546:Isoquinolines; D008024:Ligands; D010080:Oxazoles; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma
PPARs; metabolic syndrome; multitargeted agonists; side-effects; synergistic reaction; type 2 diabetes