Structural analogues of smoothened intracellular loops as potent inhibitors of hedgehog pathway and cancer cell growth
Structural analogues of smoothened intracellular loops as potent inhibitors of hedgehog pathway and cancer cell growth
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DOI：
10.1021/jm0705657
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发表时间：
2007-09-06
影响因子：
7.3
通讯作者：
Tarasova, Nadya I.
中科院分区：
文献类型：
--
作者：
Remsberg, Jarrett R.;Lou, Hong;Tarasova, Nadya I.
Smoothened是Hedgehog通路的关键组成部分，对干细胞更新至关重要，并且在许多癌症类型中失调。我们已经发现smoothened的第二和第三胞内环的合成类似物是Hedgehog途径的有效抑制剂。短至10个残基的棕榈酰化肽以低纳摩尔范围内的IC 50抑制黑素瘤细胞生长。这些化合物是有前途的候选药物和解决Hedgehog信号机制的方便工具。
Smoothened is a critical component of the Hedgehog pathway that is essential for stem cell renewal and is dysregulated in many cancer types. We have found synthetic analogues of the second and third intracellular loops of smoothened to be potent inhibitors of the Hedgehog pathway. Palmitoylated peptides as short as 10 residues inhibited melanoma cells growth with IC50 in the low nanomolar range. The compounds are promising drug candidates and convenient tools for solving mechanisms of Hedgehog signaling.