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抗微管药物

Anti-Microtubule Drugs.

作者信息

Florian Stefan, Mitchison Timothy J

机构信息

Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

出版信息

Methods Mol Biol. 2016;1413:403-21. doi: 10.1007/978-1-4939-3542-0_25.

Abstract

Small molecule drugs that target microtubules (MTs), many of them natural products, have long been important tools in the MT field. Indeed, tubulin (Tb) was discovered, in part, as the protein binding partner of colchicine. Several anti-MT drug classes also have important medical uses, notably colchicine, which is used to treat gout, familial Mediterranean fever (FMF), and pericarditis, and the vinca alkaloids and taxanes, which are used to treat cancer. Anti-MT drugs have in common that they bind specifically to Tb in the dimer, MT or some other form. However, their effects on polymerization dynamics and on the human body differ markedly. Here we briefly review the most-studied molecules, and comment on their uses in basic research and medicine. Our focus is on practical applications of different anti-MT drugs in the laboratory, and key points that users should be aware of when designing experiments. We also touch on interesting unsolved problems, particularly in the area of medical applications. In our opinion, the mechanism by which any MT drug cures or treats any disease is still unsolved, despite decades of research. Solving this problem for particular drug-disease combinations might open new uses for old drugs, or provide insights into novel routes for treatment.

摘要

靶向微管(MT)的小分子药物,其中许多是天然产物,长期以来一直是微管领域的重要工具。事实上,微管蛋白(Tb)部分是作为秋水仙碱的蛋白质结合伴侣而被发现的。几类抗微管药物也有重要的医学用途,特别是秋水仙碱,用于治疗痛风、家族性地中海热(FMF)和心包炎,以及长春花生物碱和紫杉烷,用于治疗癌症。抗微管药物的共同特点是它们特异性地结合二聚体、微管或其他形式的微管蛋白。然而,它们对聚合动力学和人体的影响却有显著差异。在这里,我们简要回顾一下研究最多的分子,并评论它们在基础研究和医学中的用途。我们的重点是不同抗微管药物在实验室中的实际应用,以及用户在设计实验时应注意的关键点。我们还会涉及一些有趣的未解决问题,特别是在医学应用领域。我们认为,尽管经过了几十年的研究,任何抗微管药物治愈或治疗任何疾病的机制仍然未得到解决。解决特定药物 - 疾病组合的这个问题可能会为旧药开辟新用途,或者为新的治疗途径提供见解。

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