Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well‐established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles. This has important implications for inhibitor development, as STs also play significant roles in immune responses, inflammation, viral infection, and neurological disorders. Thus, the current goal in order to advance to the clinic is the development of subtype selective, cell‐permeable and synthetically accessible, small‐molecule ST inhibitors. Herein is a comprehensive review of the latest developments in ST inhibitors from design, Nature, and high‐throughput screening, addressing both the challenges and opportunities in targeting cell surface sialylation. The review features an overview of the biological evaluation methods, computational and imaging tools, inhibitor molecular diversity, and selectivity toward ST subtypes, along with the emerging role of ST inhibitors as diagnostic tools for disease imaging.

中文翻译：

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唾液酸转移酶抑制剂的研究进展：治疗上的挑战和机遇

肿瘤细胞表面蛋白的过度唾液酸化以及唾液酸转移酶（ST）活性的明显上调是癌症的公认标志。由于ST在肿瘤生长和进展中的关键作用，ST抑制已成为包括胰腺癌和卵巢癌在内的一系列癌症的潜在新抗转移策略。人STs根据其连接和受体分子分为亚型，每种亚型控制具有独特生物学作用的特定唾液酸化结构的合成。这对抑制剂的开发具有重要意义，因为ST在免疫反应，炎症，病毒感染和神经系统疾病中也起着重要作用。因此，要想进入临床，当前的目标是开发亚型选择性，可渗透细胞且可合成的亚型，小分子ST抑制剂。本文从设计，性质和高通量筛选方面全面综述了ST抑制剂的最新发展，探讨了靶向细胞表面唾液酸化的挑战和机遇。综述概述了生物学评估方法，计算和成像工具，抑制剂分子多样性以及对ST亚型的选择性，以及ST抑制剂作为疾病成像诊断工具的新兴作用。