Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein. The results reveal that the compounds could decrease the Her2 protein, which explains their selectivity to Her2 over-expressed breast cancer cells. Furthermore, the compounds inhibited the chaperone activity of small chaperone protein that could stabilize Her2 protein.

化合物JCC76选择性抑制人表皮生长因子2（Her2）过度表达的乳腺癌细胞的增殖。在当前的研究中，进行了基于配体的结构优化，以生成新的类似物，我们确定了衍生物16和17，这些衍生物对Her2阳性乳腺癌细胞显示出更高的活性和选择性。总结了结构活性关系（SAR）。化合物16和17还通过蛋白质印迹测定法检查了它们对Her2蛋白的作用。结果表明，这些化合物可以降低Her2蛋白，这说明了它们对过表达的Her2乳腺癌细胞的选择性。此外，这些化合物抑制了可以稳定Her2蛋白的小分子伴侣蛋白的伴侣活性。