Sblano Sabina, Cerchia Carmen, Laghezza Antonio, Piemontese Luca, Brunetti Leonardo, Leuci Rosalba, Gilardi Federica, Thomas Aurelien, Genovese Massimo, Santi Alice, Tortorella Paolo, Paoli Paolo, Lavecchia Antonio, Loiodice Fulvio
Dipartimento Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via Orabona 4, 70125, Bari, Italy.
Dipartimento di Farmacia, "Drug Discovery" Laboratory, Università degli Studi di Napoli "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
Eur J Med Chem. 2022 May 5;235:114240. doi: 10.1016/j.ejmech.2022.114240. Epub 2022 Mar 16.
The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of the metabolic homeostasis and therefore represent valuable therapeutic targets for the treatment of metabolic diseases. The development of more balanced drugs interacting with PPARs, devoid of the side-effects showed by the currently marketed PPARγ full agonists, is considered the major challenge for the pharmaceutical companies. Here we present a chemoinformatics search approach for new ligands that let us identify a novel PPAR pan-agonist with a very attractive activity profile being able to reduce lipid accumulation and improve insulin sensitivity. This compound represents, therefore, the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes.
过氧化物酶体增殖物激活受体（PPARs）是参与调节代谢稳态的核受体，因此是治疗代谢性疾病的重要治疗靶点。开发与PPARs相互作用且无目前市售PPARγ完全激动剂所显示副作用的更平衡药物，被认为是制药公司面临的主要挑战。在此，我们提出一种用于寻找新配体的化学信息学搜索方法，该方法使我们能够鉴定出一种具有非常吸引人的活性谱的新型PPAR泛激动剂，它能够减少脂质积累并改善胰岛素敏感性。因此，这种化合物代表了一类用于治疗2型糖尿病血脂异常的新型药物的潜在先导物。
