Dipartimento di Farmacia, Università G. d'Annunzio, via dei Vestini, Chieti 66100, Italy.
Eur J Med Chem. 2012 Dec;58:317-22. doi: 10.1016/j.ejmech.2012.10.019. Epub 2012 Oct 23.
The identification of novel PPAR ligands represents an attractive research to fully understand the complex biological pathways regulated by these receptors. Selective PPAR modulators, inverse agonists and antagonists of three PPAR isoforms could help to clarify biological effects on lipid and glucose homeostasis. Here we describe the identification of a group of N-(methylsulfonyl)amides, derived from PPARα agonist carboxylic acids. Transactivation and FRET assay confirmed an antagonist behaviour on PPARα for some of these compounds, with submicromolar IC(50). A preliminary analysis on selectivity α/γ revealed different profiles of inhibition or activation.
鉴定新型过氧化物酶体增殖物激活受体 (PPAR) 配体是一项极具吸引力的研究，有助于充分了解这些受体所调控的复杂生物学途径。选择性 PPAR 调节剂、三种 PPAR 亚型的反向激动剂和拮抗剂，有助于阐明对脂质和葡萄糖内稳态的生物学影响。在这里，我们描述了一组 N-(甲基磺酰基)酰胺的鉴定，这些化合物来源于 PPARα 激动剂羧酸。转染和 FRET 检测证实，其中一些化合物对 PPARα 具有拮抗剂活性，半数抑制浓度 (IC50) 为亚微摩尔级。对选择性 α/γ 的初步分析显示出不同的抑制或激活特性。
