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

IF 3 4区 医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-07-03 DOI:10.1007/s11302-024-10031-0
R Huzaifa Sharafat, Aamer Saeed
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Abstract

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.

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外显子核苷酸酶抑制剂:靶向信号通路促进治疗--深度综述。
外显子核苷酸酶抑制剂是一系列药理药物,通过选择性地靶向外显子核苷酸酶,对改变嘌呤能信号通路至关重要。细胞外核苷酸和核苷的水解是由这些酶完成的,其中包括外切核苷三磷酸二磷酸水解酶(NTPDases)和外切-5'-核苷酸酶(CD73)。外切核苷酸酶抑制剂可通过阻断这些酶阻止 ATP 和 ADP 转化为腺苷,并减少细胞外腺苷。这些分子对于嘌呤能信号转导至关重要,而嘌呤能信号转导与各种生理和病理过程有关。通过改变细胞外核苷酸代谢和改善嘌呤能信号调节,外切核苷酸焦磷酸酶/磷酸二酯酶(ENPP)抑制剂有望改善癌症治疗、炎症控制和免疫反应调节。嘌呤能信号传导会受到 CD73 抑制剂的影响,因为它们会阻止 AMP 转化为腺苷。这些抑制剂在癌症治疗和免疫疗法中非常有用,因为它们可以提高化疗效果并改变免疫反应。嘌呤能信号传导受 NTPDase 抑制剂控制,这些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疾病和自身免疫性疾病。碱性磷酸酶(ALP)抑制剂可改变参与去磷酸化反应的酶的功能,从而对多种生物过程产生影响。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。本文通过阐明外切核苷酸酶抑制剂的过程、优势和难点,为希望在各种疾病中利用外切核苷酸酶抑制剂的补救能力的研究人员和临床医生提供了指南。
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来源期刊
Purinergic Signalling
Purinergic Signalling 医学-神经科学
CiteScore
6.60
自引率
17.10%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
期刊最新文献
Correction to: Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist. Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. Purinergic regulation of pulmonary vascular tone. Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility. Unexpected role of microglia and P2Y12 in the induction of and emergence from anesthesia.
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