Chemistry Department, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; Research Laboratories Centre, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
Chemistry Department, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; Research Laboratories Centre, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
Eur J Med Chem. 2019 Mar 15;166:502-513. doi: 10.1016/j.ejmech.2019.01.067. Epub 2019 Feb 1.
The peroxisome proliferator-activated receptors (PPAR-α, PPAR-β/δ, and PPAR-γ) are members of the nuclear receptor super-family, acting as ligand-inducible transcription factors and play crucial roles in glucose and lipid metabolism. These are a well-known receptor for diabetic therapy, not only influence the cardiovascular systems but are also expressed in many human solid tumors. For atherosclerosis, inflammation, and hypertension, the PPARs are considered as important therapeutic targets. Furthermore, it has been suggested that careful designing of partial agonists for PPARs, may show improvement with the side effects and also increase the therapeutic value for different diseases as cancer, inflammation and cardiovascular etc. This review summaries structural features of PPAR receptors, illustrates the method of PPAR modulator design, then analyzes recent dual- and pan-agonist with different therapeutic outcomes of the receptor to be used as a target for drugs in future. The advances in PPARs antagonists, their classification and structure-activity relationship are also summarized.
过氧化物酶体增殖物激活受体 (PPAR-α、PPAR-β/δ 和 PPAR-γ) 是核受体超家族的成员，作为配体诱导型转录因子发挥作用，在葡萄糖和脂质代谢中发挥关键作用。它们是糖尿病治疗的知名靶点，不仅影响心血管系统，而且在许多人类实体瘤中也有表达。对于动脉粥样硬化、炎症和高血压，PPAR 被认为是重要的治疗靶点。此外，有人提出，对 PPAR 进行部分激动剂的精心设计，可能会改善副作用，并提高针对不同疾病（如癌症、炎症和心血管疾病等）的治疗价值。本文综述了 PPAR 受体的结构特征，说明了 PPAR 调节剂设计的方法，然后分析了最近具有不同治疗效果的双激动剂和全激动剂，将它们作为未来药物的靶点。还总结了 PPAR 拮抗剂的进展、分类和结构-活性关系。
