Ras proteins are small GTPases which regulate cellular proliferation, differentiation, and apoptosis. Constitutively active mutant Ras are expressed in ~15-20% human cancers, and K-Ras mutations account for ~85% of all Ras mutations. Despite the significance of Ras proteins in refractory cancers, there is no anti-Ras drug available in clinic. Since K-Ras must interact with the plasma membrane (PM) for biological activity, inhibition of the K-Ras/PM interaction is a tractable approach to block oncogenic K-Ras activity. Here, we discovered chalcones 1 and 8 exhibit anti-K-Ras activity, and show that the compounds mislocalize K-Ras from the PM and block oncogenic K-Ras signal output. Also, 1 inhibits the growth of K-Ras-driven human cancer cells. Our data suggest that 1 could be a promising starting point for developing anti-K-Ras cancer drug.

中文翻译：

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带有3,4,5-三甲氧基苯基基序的查耳酮能够选择性抑制致癌的K-Ras信号传导。

Ras蛋白是小的GTPases，可调节细胞增殖，分化和凋亡。组成型活性突变型Ras在约15-20％的人类癌症中表达，K-Ras突变占所有Ras突变的〜85％。尽管Ras蛋白在难治性癌症中具有重要意义，但临床上尚无抗Ras药物。由于K-Ras必须与质膜（PM）相互作用才能发挥生物学活性，因此抑制K-Ras / PM相互作用是阻止致癌K-Ras活性的一种容易处理的方法。在这里，我们发现查耳酮1和8表现出抗K-Ras活性，并表明该化合物使PM中的K-Ras错位并阻止了致癌的K-Ras信号输出。同样，1抑制K-Ras驱动的人类癌细胞的生长。我们的数据表明1可能是开发抗K-Ras癌症药物的有希望的起点。