沙利度胺衍生免疫调节药物(IMiDs)作为潜在的治疗剂。

J Blake Marriott, Keith Dredge, Angus G Dalgleish
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引用次数: 17

摘要

已知沙利度胺对治疗多种疾病有效,包括麻风病和各种癌症。确切的作用机制尚不清楚,尽管已知这些包括抗肿瘤坏死因子(TNF)- α, T细胞共刺激,抗血管生成和抗肿瘤活性。然而,沙利度胺正在被新的结构衍生物所取代,这些衍生物被设计成具有更好的免疫调节活性和副作用。这些疾病目前正在进行鉴定,其中一些正在进入临床I/II期研究。一类新的结构类似物被归类为免疫调节药物(IMiDs)。本文综述了沙利度胺的免疫学、抗血管生成和直接抗肿瘤特性,以及其IMiD类似物的特性和临床应用。我们描述了实验室研究,这些研究导致了IMiDs的特征和发展成为潜在的临床相关药物。早期试验数据表明,这些化合物本身可能成为既定的治疗方法,特别是在某些癌症中。此外,正在进行的研究将确定如何最好地将这些化合物应用于适当的临床环境。我们将描述正在进行的各种先导化合物的临床研究,并推测这些令人兴奋的化合物的潜力和未来的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Thalidomide derived immunomodulatory drugs (IMiDs) as potential therapeutic agents.

Thalidomide is known to be effective in the treatment of a number of conditions, including leprosy and various cancers. The exact mechanisms of action remain unclear although these are known to include anti-tumour necrosis factor (TNF)-alpha, T cell costimulatory, anti-angiogenic and anti-tumour activities. However, thalidomide is being superceded by novel structural derivatives which have been designed to have improved immunomodulatory activity and side effect profiles. These are currently being characterised and some are entering the clinic in phase I/II studies. One novel group of structural analogues are classified as the Immunomodulatory Drugs (IMiDs). This review describes the emerging immunological, anti-angiogenic and direct anti-tumour properties of thalidomide and the characterisation and clinical application of its IMiD analogues. We describe the laboratory studies which have led to the characterisation and development of IMiDs into potentially clinically relevant drugs. Early trial data suggests that these compounds may themselves become established therapies, particularly in certain cancers. Furthermore, ongoing studies will determine how best to apply these compounds to the appropriate clinical settings. We will describe the various clinical studies of lead compounds that are in progress and speculate as to the potential and future development of these exciting compounds.

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