研究动态
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外核苷酸酶抑制剂:针对治疗进展的信号通路 - 深入综述。

Ectonucleotidase inhibitors: targeting signaling pathways for therapeutic advancement-an in-depth review.

发表日期:2024 Jul 03
作者: R Huzaifa Sharafat, Aamer Saeed
来源: Bone & Joint Journal

摘要:

外切核苷酸酶抑制剂是一类药理学药物,通过选择性地靶向外切核苷酸酶,对于改变嘌呤能信号通路至关重要。胞外核苷酸和核苷的水解是由这些酶进行的,其中包括外核苷三磷酸二磷酸水解酶(NTPDases)和外切5'-核苷酸酶(CD73)。外核苷酸酶抑制剂可以通过阻断这些酶并减少细胞外腺苷来阻止 ATP 和 ADP 转化为腺苷。这些分子对于嘌呤能信号传导至关重要,嘌呤能信号传导与生理和病理过程的变异性相关。通过改变细胞外核苷酸代谢和改善嘌呤能信号调节,外核苷酸焦磷酸酶/磷酸二酯酶 (ENPP) 抑制剂有可能改善癌症治疗、炎症管理和免疫反应调节。嘌呤能信号传导受到 CD73 抑制剂的影响,因为它们阻止 AMP 转化为腺苷。这些抑制剂可用于癌症治疗和免疫治疗,因为它们可以提高化疗效果并改变免疫反应。嘌呤能信号传导由 NTPDase 抑制剂控制,该抑制剂专门针对参与细胞外核苷酸分解的酶。这些抑制剂有望减少免疫反应、血栓形成和炎症,或许有助于治疗心血管和自身免疫性疾病。碱性磷酸酶 (ALP) 抑制剂会改变参与去磷酸化反应的酶的功能,从而影响多种生物过程。通过改变体内的磷酸盐水平,这些抑制剂可用于治疗包括高磷血症和某些骨骼问题在内的疾病。本文通过阐明外核苷酸酶抑制剂的治疗过程、优点和困难,为希望在各种疾病情况下利用核酸外切核苷酸酶抑制剂的治疗能力的研究人员和临床医生提供了指南。© 2024。作者获得 Springer Nature B.V. 的独家许可。
Ectonucleotidase inhibitors are a family of pharmacological drugs that, by selectively targeting ectonucleotidases, are essential in altering purinergic signaling pathways. The hydrolysis of extracellular nucleotides and nucleosides is carried out by these enzymes, which include ectonucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (CD73). Ectonucleotidase inhibitors can prevent the conversion of ATP and ADP into adenosine by blocking these enzymes and reduce extracellular adenosine. These molecules are essential for purinergic signaling, which is associated with a variability of physiological and pathological processes. By modifying extracellular nucleotide metabolism and improving purinergic signaling regulation, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) inhibitors have the potential to improve cancer treatment, inflammatory management, and immune response modulation. Purinergic signaling is affected by CD73 inhibitors because they prevent AMP from being converted to adenosine. These inhibitors are useful in cancer therapy and immunotherapy because they may improve chemotherapy effectiveness and alter immune responses. Purinergic signaling is controlled by NTPDase inhibitors, which specifically target enzymes involved in extracellular nucleotide breakdown. These inhibitors show promise in reducing immunological responses, thrombosis, and inflammation, perhaps assisting in the treatment of cardiovascular and autoimmune illnesses. Alkaline phosphatase (ALP) inhibitors alter the function of enzymes involved in dephosphorylation reactions, which has an impact on a variety of biological processes. By altering the body's phosphate levels, these inhibitors may be used to treat diseases including hyperphosphatemia and certain bone problems. This article provides a guide for researchers and clinicians looking to leverage the remedial capability of ectonucleotidase inhibitors in a variety of illness scenarios by illuminating their processes, advantages, and difficulties.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.