沙利度胺及其衍生物临床及作用机制研究进展

The clinical application and mechanisms evolution of thalidomide and its derivatives

沙利度胺是一种合成的谷氨酸衍生物,原作为镇静剂治疗早孕反应,20世纪60年代出现严重的胎儿缺陷而被禁止使用。但此后研究发现,沙利度胺具有免疫调节和抗血管生成作用,治疗多发性骨髓瘤等恶肿瘤以及其他难治性疾病有效。通过对沙利度胺进行结构改造得到的一系列免疫调节药克服了原形药物的严不良反应,这些药物的强大的抗癌作用意味着它们将走出沙利度胺的阴影,成为有效的抗肿瘤药物。现对沙利胺及其衍生物的临床应用和作用机制的研究进展进行综述。

Thalidomide, a synthetic glutamic-acid derivative, was originally designed to treat morning sickness and removed from the marketing in the early 1960s due to its serious congenital birth defects. Recent studies found that thalidomide has potential anti-inflammatory and anticancer activities, including the treatment of relapsed multiple myeloma （MM） and other refractory diseases. Structural modifications of thalidomide have led to a series of new agents that get rid of the devastating teratogenicity. The powerful anticancer activities of such new derivatives are breaking them away from the notorious reputation of thalidomide. This article highlights the mechanisms and clinical applications of new thalidomide derivatives.