Degradation of intracellular TGF-β1 by PROTACs efficiently reverses M2 macrophage induced malignant pathological events

Yanqiao Feng; Hui Su; Yunzhi Li; Chunxiang Luo; Huiying Xu; Youqiao Wang; Haixia Sun; Guohui Wan; Binhua Zhou; Xianzhang Bu

doi:10.1039/c9cc08391j

Degradation of intracellular TGF-β1 by PROTACs efficiently reverses M2 macrophage induced malignant pathological events

Chem Commun (Camb). 2020 Mar 5;56(19):2881-2884. doi: 10.1039/c9cc08391j.

Authors

Affiliations

¹ School of Pharmaceutical Sciences, Sun Yat-sen University, GuangZhou 510006, China. zhoubh5@mail.sysu.edu.cn phsbxzh@mail.sysu.edu.cn.
² School of Pharmaceutical Sciences, Sun Yat-sen University, GuangZhou 510006, China. zhoubh5@mail.sysu.edu.cn phsbxzh@mail.sysu.edu.cn and School of Chinese Pharmacy, Guizhou Minzu University, Guiyang 550025, China.

PMID: 32037404
DOI: 10.1039/c9cc08391j

Abstract

The first proteolysis targeting chimeras for the intracellular elimination of transforming growth factor-β1 (TGF-β1), which contributes to various diseases, are described. The appropriately designed DT-6 could efficiently degrade intracellular TGF-β1, and inhibit M2 macrophage induced epithelial to mesenchymal transition and invasive migration of cancer cells.

MeSH terms

Epithelial-Mesenchymal Transition
Hep G2 Cells
Humans
Intercellular Signaling Peptides and Proteins / metabolism*
Macrophages / metabolism*
Neoplasm Invasiveness
Transforming Growth Factor beta1 / metabolism*

Substances

Intercellular Signaling Peptides and Proteins
TGFB1 protein, human
Transforming Growth Factor beta1
snake venom protein C activator