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N-acylethanolamine hydrolyzing acid amidase inhibition: tools and potential therapeutic opportunities
Drug Discovery Today ( IF 6.5 ) Pub Date : 2018-03-19 , DOI: 10.1016/j.drudis.2018.03.007
Pauline Bottemanne , Giulio G. Muccioli , Mireille Alhouayek

N-acylethanolamines (NAEs) (e.g., N-palmitoylethanolamine, N-arachidonoylethanolamine, N-oleoylethanolamine) are bioactive lipids involved in many physiological processes including pain, inflammation, anxiety, cognition and food intake. Two enzymes are responsible for the hydrolysis of NAEs and therefore regulate their endogenous levels and effects: fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA). As discussed here, extensive biochemical characterization of NAAA was carried out over the years that contributed to a better understanding of NAAA enzymology. An increasing number of studies describe the synthesis and pharmacological characterization of NAAA inhibitors. Recent medicinal chemistry efforts have led to the development of potent and stable inhibitors that enable studying the effects of NAAA inhibition in preclinical disease models, notably in the context of pain and inflammation.



中文翻译:

N-酰基乙醇胺水解酸酰胺酶抑制:工具和潜在的治疗机会

N-酰基乙醇胺(NAE)(例如,N-棕榈酰乙醇胺,N-花生四烯酰基乙醇胺,N-油酰乙醇胺)是涉及许多生理过程的生物活性脂质,包括疼痛,炎症,焦虑,认知和食物摄入。两种酶负责NAE的水解,因此调节其内源性水平和作用:脂肪酸酰胺水解酶(FAAH)和N-酰基乙醇胺-水解酸酰胺酶(NAAA)。如本文所述,多年来,对NAAA进行了广泛的生化表征,这有助于更好地理解NAAA酶学。越来越多的研究描述了NAAA抑制剂的合成和药理学表征。最近的药物化学努力已导致开发出有效且稳定的抑制剂,从而能够研究NAAA抑制在临床前疾病模型中的作用,特别是在疼痛和炎症的情况下。

更新日期:2018-03-19
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