Discovery and biological evaluation of carborane-containing derivatives as TEAD auto palmitoylation inhibitors.

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Tác giả: Guanxiang Hao, Yundong He, Chaofan Li, Hongjing Li, Yuxuan Song, Nan Sun, Linyuan Wang, Sinan Wang, Changxian Yuan, Yingshuang Zhang, Yirong Zhang, Zhiguang Zhang, Ziyin Zhang

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Bioorganic & medicinal chemistry letters , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 738803

Transcriptional enhanced associate domain (TEAD) proteins are key downstream effectors of the Hippo signaling pathway that play a crucial role in various cell processes including tissue development, regeneration, cell proliferation and cancer. TEADs contain a hydrophobic auto-palmitoylation pocket that can bind palmitic acid and stabilize TEADs from being degraded. Inhibitors targeting this palmitoylation pocket typically consist of hydrophobic pharmacophores. Carboranes is a cage-shaped molecule exhibiting superior hydrophobicity compared to adamantane or phenyl groups. Herein, we incorporated carborane into known TEAD inhibitors for better interaction with the hydrophobic palmitate pocket. Compounds 1f and 1l are identified as TEAD transcription inhibitors with strong anti-proliferation and anti-migration activities toward prostate cancer cell lines. They also significantly reduced TEAD-regulated downstream gene expressions.
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