Chemistry and biology of wortmannin
Chemistry and biology of wortmannin
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DOI：
10.1039/b504418a
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Halter, RJ
中科院分区：
文献类型：
--
作者：
Wipf, P;Halter, RJ
最近对绿素类甾体呋喃的合成和生物学研究揭示了基础发现和先进药物设计的多种机会。Wortmannin是一种有效的酶抑制剂，能与PI-3和Polo样激酶等重要调节蛋白的ATP位点结合。该天然产物与其他绿素具有共同的独特的基于机理的生物激活途径。此外，虽然已经有几种令人鼓舞的方法来全面合成这些化合物，但在合成战略和战术方面仍有很大的改进空间，开发结构简化的类似物具有更具体的生物效应，并且没有阻碍母体化合物临床开发的毒性问题。
Recent synthetic and biological studies of the viridin class of steroidal furans have revealed multiple opportunities for fundamental discoveries as well as advanced drug design. Wortmannin is a potent enzyme inhibitor that binds to the ATP site of important regulatory kinases such as PI-3 kinase and Polo-like kinase. The natural product shares a unique mechanism-based biological activation pathway with other viridins. Furthermore, while there have been several encouraging approaches toward the total synthesis of these compounds, there is still ample room for improvements in synthetic strategies and tactics, and the development of structurally simplified analogs that exert more specific biological effects and are devoid of toxicity issues that have thwarted the clinical development of the parent compounds.