Identification of the HECT domain binding of indole-3-carbinol (I3C) derivatives for breast cancer therapy
Wenwen Zheng, Zhichao Shi, Xun Zhang, Weibin Wu, Zigao Yuan, Lei Zhao, Qinyuan Li, Zixuan Qiu, Cunlong Zhang, Bizhu Chu, Zijian Liu, Wei-Min Chen, Yuyang Jiang
Journal：Phytochemistry Letters
IF：1.7
DOI：10.1016/j.phytol.2023.01.002
PMID：
Published：2023-01-17
research field：分子生物学毒理学内分泌学环境健康
Abstract
We designed and synthesized a series of HECT (homologous to the E6-AP carboxyl terminus) domain binding inhibitors based on indole-3-carbinol (I3C) by structure-based rational drug design . Thermal shift and MTT assays indicated that compound A3 had a good HECT domain binding capacity and potent breast cancer cells inhibition activity, respectively. Subsequent studies showed that compound A3 inhibited proliferation and invasion, induced apoptosis and S-phase cell block. Additionally, compound A3 altered the expression of apoptosis and cell cycle related protein in MDA-MB-231 cells. Finally, computational simulation indicated the proposed binding mode of A3 with the NEDD4–1 HECT domain.
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