Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review, we provide in-depth information on various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase which are associated with various types of cancers. We also discuss the physicochemical properties of well-studied inhibitors with natural product origins and their related structures in terms of these enzymes. Targeting ceramide metabolism exhibited promising mono- and combination therapies at preclinical stages in preventing cancer progression and cemented the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels.
多年来，分子靶向策略已被用于控制癌症进展，其基础通常是靶向代谢途径中的各种酶。基于此，明确每种酶在特定代谢途径中的作用至关重要。本综述深入探讨了与多种癌症相关的酶类，包括神经酰胺酶、鞘氨醇激酶、鞘磷脂合酶、二氢神经酰胺去饱和酶及神经酰胺合酶。同时，系统阐述了天然产物来源的经典抑制剂的理化特性及其针对这些酶的相关结构。靶向神经酰胺代谢在临床前研究中展现出单药及联合疗法在抑制癌症进展方面的潜力，进一步确立了鞘脂代谢在癌症治疗中的重要意义。针对神经酰胺代谢酶的靶向研究，将有助于药物化学家设计出高效、选择性强的活性小分子，从不同层面干预癌症进展。
肿瘤(癌症)患者之家