摘要
沙利度胺是具有有趣治疗特性的药物,但也有严重的副作用,需要仔细和监测使用。潜在的免疫调节,抗炎,抗血管生成和镇静作用使沙利度胺成为治疗多种疾病如多发性骨髓瘤的良好候选药物。通过增加TNFα-mRNA的降解,沙利度胺通过脂多糖或由有丝分裂刺激诱导的T淋巴细胞刺激的单核细胞和巨噬细胞减少TNFα的产生。降低的TNFα水平通过阻止NF-kB的激活和减少参与细胞增殖,炎症,血管发生和保护细胞凋亡的蛋白质,特别是IL-6的合成来改变细胞内转导的机制。此外,沙利度胺通过下调其表达影响VEGF水平。如今,新的更安全和毒性较小的药物,沙利度胺的类似物正在出现,可用于更有针对性地治疗多发性骨髓瘤和其他几种疾病,如克罗恩病,类风湿性关节炎,结节病,红斑性红斑,移植物抗宿主病。
关键词: 沙利度胺,血管发生,TNF-α,IL-6,VEGF,沙利度胺类似物
Current Medicinal Chemistry
Title:A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma
Volume: 24 Issue: 25
关键词: 沙利度胺,血管发生,TNF-α,IL-6,VEGF,沙利度胺类似物
摘要: Thalidomide is a drug with interesting therapeutic properties but also with severe side effects which require a careful and monitored use. Potential immunomodulatory, antiinflammatory, anti-angiogenic and sedative properties make thalidomide a good candidate for the treatment of several diseases such as multiple myeloma. Through an increase in the degradation of TNFα-mRNA, thalidomide reduces the production of TNFα by monocytes and macrophages stimulated by lipopolysaccharide or by T lymphocytes induced by mitogenic stimuli. The decreased level of TNFα alters the mechanisms of intracellular transduction by preventing the activation of NF-kB and by decreasing the synthesis of proteins, in particular IL-6, involved in cell proliferation, inflammation, angiogenesis and protection from apoptosis. Furthermore, thalidomide affects VEGF levels by down-regulating its expression. Nowadays, new safer and less toxic drugs, analogs of thalidomide, are emerging as beneficial for a more targeted treatment of multiple myeloma and several other diseases such as Crohn's disease, rheumatoid arthritis, sarcoidosis, erythema nodosum leprosum, graft-versus-host disease.
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A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma, Current Medicinal Chemistry 2017; 24 (25) . https://dx.doi.org/10.2174/0929867324666170601074646
DOI https://dx.doi.org/10.2174/0929867324666170601074646 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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