Ceramides are composed of a sphingosine and a single fatty acid connected by an amide linkage. As one of the major classes of biologically active lipids, ceramides and their upstream and downstream metabolites have been implicated in several pathological conditions including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation. Consequently, tremendous efforts have been devoted to deciphering the dynamics of metabolic pathways involved in ceramide biosynthesis. Given that several distinct enzymes can produce ceramide, different enzyme targets have been pursued depending on the underlying disease mechanism. The main objective of this review is to provide a comprehensive overview of small molecule inhibitors reported to date for each of these ceramide-producing enzymes from a medicinal chemistry perspective.

中文翻译：

---

针对神经酰胺生物合成的小分子抑制剂，神经酰胺是鞘脂网络的中心枢纽

神经酰胺由鞘氨醇和通过酰胺键连接的单一脂肪酸组成。作为主要的生物活性脂质之一，神经酰胺及其上游和下游代谢物与多种病理状况有关，包括癌症、神经退行性变、糖尿病、微生物发病机制、肥胖和炎症。因此，人们付出了巨大的努力来破译神经酰胺生物合成中涉及的代谢途径的动力学。鉴于几种不同的酶可以产生神经酰胺，因此根据潜在的疾病机制追求不同的酶靶点。本综述的主要目的是从药物化学角度全面概述迄今为止报道的每种神经酰胺生成酶的小分子抑制剂。