Chemical 'Jekyll and Hyde's: small-molecule inhibitors of developmental signaling pathways.
Chemical 'Jekyll and Hyde's: small-molecule inhibitors of developmental signaling pathways.
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DOI：
10.1039/c1cs15019g
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发表时间：
2011-08
影响因子：
46.2
通讯作者：
Chen JK
中科院分区：
文献类型：
--
作者：
Sakata T;Chen JK
干扰发育信号通路的小分子可以对胚胎模式产生毁灭性的影响，正如20世纪50年代化学诱导的独眼羔羊和四肢严重缩短的儿童的发病所证明的那样。然而，最近的研究揭示了这些途径在人类疾病和疾病中的关键作用，促使人们重新审视这些化合物作为新的靶向治疗方法。在本教程综述中，我们描述了四个致畸化合物的案例研究，包括刺猬蛋白（Hh）、Wnt和骨形态发生蛋白（BMP）途径的抑制剂。我们讨论了这些致畸原是如何被发现的，它们的作用机制，它们作为分子探针的效用，以及它们作为治疗剂的潜力。我们还考虑了该领域当前面临的挑战和未来研究的可能方向。
Small molecules that perturb developmental signaling pathways can have devastating effects on embryonic patterning, as evidenced by the chemically induced onset of cyclopic lambs and children with severely shortened limbs during the 1950s. Recent studies, however, have revealed critical roles for these pathways in human disorders and diseases, spurring the re-examination of these compounds as new targeted therapies. In this tutorial review, we describe four case studies of teratogenic compounds, including inhibitors of the Hedgehog (Hh), Wnt, and bone morphogenetic protein (BMP) pathways. We discuss how these teratogens were discovered, their mechanisms of action, their utility as molecular probes, and their potential as therapeutic agents. We also consider current challenges in the field and possible directions for future research.
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影响因子：
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作者：
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Zon LI
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