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硫唑嘌呤(AZA)在病毒、风湿和皮肤疾病中的当代及前瞻性应用:药物基因组学和纳米技术应用综述

Contemporary and prospective use of azathioprine (AZA) in viral, rheumatic, and dermatological disorders: a review of pharmacogenomic and nanotechnology applications.

作者信息

Rathi Gulshan, Shamkuwar Prashant B, Rathi Karishma, Ranazunjare Ruchita, Kulkarni Soham

机构信息

Department of Pharmaceutics, VSS Institute of Pharmacy, Badnapur, Maharashtra, India.

Department of Pharmacognosy, Government College of Pharmacy, Chhatrapati Sambhajinagar, Maharashtra, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3183-3197. doi: 10.1007/s00210-024-03569-8. Epub 2024 Nov 4.

DOI:10.1007/s00210-024-03569-8
PMID:39495265
Abstract

Azathioprine (AZA) has been extensively used for immunomodulatory effects in autoimmune disorders and transplantation. This article is proposed to review the contemporary and prospective use of AZA in viral, rheumatic, and dermatological disorders. The primary objective is to draw attention to possible developments in regards to AZA application in recent years, with an emphasis on the use of pharmacogenomics and nanotechnology to improve its efficacy in practice. This study reveals that AZA, having the active metabolites 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), may be useful in the treatment of systemic lupus erythematosus (SLE), pemphigus vulgaris, and psoriasis. Pharmacogenomic testing of thiopurine methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) genotypes minimizes the occurrence of myelosuppression. Furthermore, new formulations of AZA using biocompatible polymers and nanoparticles for drug delivery were reported to improve its efficacy and lower systemic toxicity. This paper aims to establish the multifunctional nature of AZA in modern medicine, thus emphasizing its potential for other applications. Through the combination of pharmacogenomic analysis along with nanotechnology application, AZA makes the promise of enhancing patients' treatment efficacy and extending the stock of medical information available. These advancements offer new possibilities for application of precision medicine and improvements in the use of AZA therapy.

摘要

硫唑嘌呤(AZA)已被广泛用于自身免疫性疾病和移植中的免疫调节作用。本文旨在综述AZA在病毒、风湿和皮肤病中的当代及未来应用。主要目的是提请关注近年来AZA应用的可能进展,重点是利用药物基因组学和纳米技术提高其在实际应用中的疗效。本研究表明,具有活性代谢产物6-巯基嘌呤(6-MP)和6-硫鸟嘌呤(6-TG)的AZA可能对系统性红斑狼疮(SLE)、寻常型天疱疮和银屑病的治疗有用。硫嘌呤甲基转移酶(TPMT)和Nudix水解酶15(NUDT15)基因型的药物基因组学检测可将骨髓抑制的发生率降至最低。此外,据报道,使用生物相容性聚合物和纳米颗粒进行药物递送的AZA新制剂可提高其疗效并降低全身毒性。本文旨在确立AZA在现代医学中的多功能性质,从而强调其在其他应用中的潜力。通过药物基因组学分析与纳米技术应用相结合,AZA有望提高患者的治疗效果并增加可用的医学信息储备。这些进展为精准医学的应用和AZA治疗的改进提供了新的可能性。

相似文献

1
Contemporary and prospective use of azathioprine (AZA) in viral, rheumatic, and dermatological disorders: a review of pharmacogenomic and nanotechnology applications.硫唑嘌呤(AZA)在病毒、风湿和皮肤疾病中的当代及前瞻性应用:药物基因组学和纳米技术应用综述
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3183-3197. doi: 10.1007/s00210-024-03569-8. Epub 2024 Nov 4.
2
Thiopurine methyltransferase genotype and the toxicity of azathioprine in Japanese.硫嘌呤甲基转移酶基因型与硫唑嘌呤在日本人中的毒性。
Intern Med. 1999 Dec;38(12):944-7. doi: 10.2169/internalmedicine.38.944.
3
and Genetic Polymorphisms Are Related to Azathioprine Intolerance in Chinese Patients with Rheumatic Diseases.并且基因多态性与中国风湿性疾病患者对硫唑嘌呤不耐受有关。
Genet Test Mol Biomarkers. 2019 Oct;23(10):751-757. doi: 10.1089/gtmb.2018.0313. Epub 2019 Sep 26.
4
Azathioprine-induced fatal myelosuppression in systemic lupus erythematosus patient carrying TPMT*3C polymorphism.携带TPMT*3C基因多态性的系统性红斑狼疮患者中硫唑嘌呤诱导的致命性骨髓抑制。
Lupus. 2008 Feb;17(2):132-4. doi: 10.1177/0961203307085255.
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Current use of pharmacogenetic testing: a national survey of thiopurine methyltransferase testing prior to azathioprine prescription.药物遗传学检测的当前应用:一项关于硫唑嘌呤处方前硫嘌呤甲基转移酶检测的全国性调查。
J Clin Pharm Ther. 2007 Apr;32(2):187-95. doi: 10.1111/j.1365-2710.2007.00805.x.
6
Pharmacogenomic Assessment of Genes Implicated in Thiopurine Metabolism and Toxicity in a UK Cohort of Pediatric Patients With Inflammatory Bowel Disease.英国炎性肠病儿科患者队列中硫嘌呤代谢及毒性相关基因的药物基因组学评估
Inflamm Bowel Dis. 2025 Feb 6;31(2):362-375. doi: 10.1093/ibd/izae126.
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The impact of thiopurine-S-methyltransferase genotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.硫嘌呤甲基转移酶基因型对炎症性肠病患者使用硫唑嘌呤产生药物不良反应的影响。
Bratisl Lek Listy. 2013;114(4):199-205. doi: 10.4149/bll_2013_042.
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Thiopurine S-methyltransferase polymorphisms and the relationship between the mutant alleles and the adverse effects in systemic lupus erythematosus patients taking azathioprine.硫嘌呤S-甲基转移酶基因多态性以及服用硫唑嘌呤的系统性红斑狼疮患者中突变等位基因与不良反应之间的关系。
Clin Exp Rheumatol. 2005 Nov-Dec;23(6):873-6.
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Choice of azathioprine or 6-mercaptopurine dose based on thiopurine methyltransferase (TPMT) activity to avoid myelosuppression. A prospective study.基于硫嘌呤甲基转移酶(TPMT)活性选择硫唑嘌呤或6-巯基嘌呤剂量以避免骨髓抑制。一项前瞻性研究。
Hepatogastroenterology. 2006 May-Jun;53(69):399-404.
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Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.临床药物遗传学实施联盟噻嘌呤甲基转移酶基因型和巯嘌呤剂量指南。
Clin Pharmacol Ther. 2011 Mar;89(3):387-91. doi: 10.1038/clpt.2010.320. Epub 2011 Jan 26.

本文引用的文献

1
Antiviral Potential of Azathioprine and Its Derivative 6- Mercaptopurine: A Narrative Literature Review.硫唑嘌呤及其衍生物6-巯基嘌呤的抗病毒潜力:一篇叙述性文献综述
Pharmaceuticals (Basel). 2024 Jan 30;17(2):174. doi: 10.3390/ph17020174.
2
Azathioprine dose tailoring based on pharmacogenetic information: Insights of clinical implementation.基于药物遗传学信息的巯嘌呤剂量调整:临床实施的见解。
Biomed Pharmacother. 2023 Dec;168:115706. doi: 10.1016/j.biopha.2023.115706. Epub 2023 Oct 17.
3
Polymer-Based Nanoparticles as Drug Delivery Systems for Purines of Established Importance in Medicine.
基于聚合物的纳米颗粒作为医学上已确立重要性的嘌呤类药物递送系统。
Nanomaterials (Basel). 2023 Sep 26;13(19):2647. doi: 10.3390/nano13192647.
4
Long-term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real-world experience.硫唑嘌呤在炎症性肠病治疗中的长期安全性和有效性:一项真实世界研究。
JGH Open. 2023 Aug 10;7(9):599-609. doi: 10.1002/jgh3.12955. eCollection 2023 Sep.
5
Commensal bacteria promote azathioprine therapy failure in inflammatory bowel disease via decreasing 6-mercaptopurine bioavailability.共生菌通过降低 6-巯基嘌呤生物利用度促进炎症性肠病的巯嘌呤治疗失败。
Cell Rep Med. 2023 Aug 15;4(8):101153. doi: 10.1016/j.xcrm.2023.101153.
6
Azathioprine monotherapy withdrawal in inflammatory bowel diseases: A retrospective mono-centric study.炎症性肠病中单用硫唑嘌呤治疗的撤药:一项回顾性单中心研究。
World J Gastroenterol. 2023 Jul 21;29(27):4334-4343. doi: 10.3748/wjg.v29.i27.4334.
7
Drug rediscovery in gastroenterology: from off-label to on-label use of thioguanine in inflammatory bowel disease.胃肠病学中的药物再发现:硫鸟嘌呤从超适应证使用到炎症性肠病的适应证内使用。
Gut. 2023 Oct;72(10):1985-1991. doi: 10.1136/gutjnl-2023-329679. Epub 2023 Jun 28.
8
6-Mercaptopurine potently inhibits recruitment of SHP2 by phosphorylated PD-1 to inhibit PD-1 signalling and enhance T cell function.6-巯基嘌呤通过磷酸化 PD-1 强烈抑制 SHP2 的募集,从而抑制 PD-1 信号通路并增强 T 细胞功能。
Immunology. 2023 Oct;170(2):230-242. doi: 10.1111/imm.13671. Epub 2023 Jun 1.
9
Childhood Pemphigus Vulgaris during COVID-19 Outbreak Successfully Treated with Prednisone and Azathioprine: A Case Report and Literature Review.新冠疫情期间儿童寻常型天疱疮采用泼尼松和硫唑嘌呤成功治疗:一例报告及文献综述
J Clin Med. 2022 Nov 21;11(22):6858. doi: 10.3390/jcm11226858.
10
Influence of the Photodegradation of Azathioprine on DNA and Cells.硫唑嘌呤的光降解对 DNA 和细胞的影响。
Int J Mol Sci. 2022 Nov 20;23(22):14438. doi: 10.3390/ijms232214438.