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药物再定位的成功案例:沙利度胺的治疗应用和作用机制的再定位。

A drug repositioning success: The repositioned therapeutic applications and mechanisms of action of thalidomide.

机构信息

Department of Pharmacy, College of Medicine and Health Sciences, 256197Wollo University, Dessie, Ethiopia.

出版信息

J Oncol Pharm Pract. 2021 Apr;27(3):673-678. doi: 10.1177/1078155220975825. Epub 2020 Nov 29.

Abstract

BACKGROUND

Thalidomide is the most teratogenic human medicine ever marketed and was associated with birth defects in approximately 10,000 children in the 1960s. The pharmacological effects of thalidomide are attributed to its anti-angiogenic, anti-inflammatory and modulatory effect on cytokines principally tumor necrosis factor-α, while the teratogenic effects are linked to two molecular targets, namely cereblon and tubulin. Teratogenicity is the gravest adverse effect of thalidomide depending on the dose and time of exposure. Nonetheless, with System for Thalidomide Education and Prescribing Safety program, the possibility of teratogenicity can be completely avoided. The sensitive period during pregnancy for thalidomide teratogenicity in humans is approximately 20-34 days after fertilization.

METHODS

Relevant articles were identified from Google scholar and PubMed (MEDLINE) using different search strategies.

CONCLUSION

Clinical trials showed that thalidomide has been found effective in the treatment of advanced renal cancer, esophageal cancer, chemotherapy refractory endometrial cancer and pancreatic cancer, which can suggest its future therapeutic potential in cancer treatment. Thalidomide is also used in the treatment of inflammatory skin disorders and has shown promising effect in the treatment of autoimmune disorders and inflammatory bowel disease. Despite thalidomide being a renowned teratogen and neurotoxin, it has been successfully repositioned and FDA approved for the treatment of erythema nodosum leprosum and multiple myeloma under strict control.

摘要

背景

沙利度胺是有史以来上市的最致畸的人类药物,在 20 世纪 60 年代,它与大约 10000 名儿童的出生缺陷有关。沙利度胺的药理作用归因于其抗血管生成、抗炎和对细胞因子(主要是肿瘤坏死因子-α)的调节作用,而致畸作用与两个分子靶点有关,即 cereblon 和微管蛋白。致畸性是沙利度胺最严重的不良反应,取决于剂量和暴露时间。尽管如此,通过沙利度胺教育和处方安全计划系统,完全可以避免致畸性的可能性。人类沙利度胺致畸的敏感期大约在受精后 20-34 天。

方法

使用不同的搜索策略,从 Google scholar 和 PubMed(MEDLINE)中确定了相关文章。

结论

临床试验表明,沙利度胺已被发现对晚期肾癌、食管癌、化疗耐药性子宫内膜癌和胰腺癌有效,这表明它在癌症治疗方面具有潜在的治疗前景。沙利度胺还用于治疗炎症性皮肤疾病,并在治疗自身免疫性疾病和炎症性肠病方面显示出良好的疗效。尽管沙利度胺是一种著名的致畸剂和神经毒素,但在严格控制下,它已被成功重新定位并获得美国食品和药物管理局批准用于治疗结节性红斑狼疮和多发性骨髓瘤。

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