2. Academic Validation
  3. Discovery of selective platelet-derived growth factor receptor-beta (PDGFR-β) bifunctional small-molecule degraders

Discovery of selective platelet-derived growth factor receptor-beta (PDGFR-β) bifunctional small-molecule degraders

  • Bioorg Med Chem. 2023 Jan 1:77:117115. doi: 10.1016/j.bmc.2022.117115.
Ru Si 1,  Nanxin Liu 1,  Jin Wang 1,  Qingqing Zhang 1,  Yanchen Li 1,  Xiaoyan Pan 1,  Jie Zhang 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
  • 2 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: zhj8623@mail.xjtu.edu.cn.
PMID: 36508995 DOI: 10.1016/j.bmc.2022.117115
Abstract

Proteolysis-targeting chimeras (PROTACs) is a promising strategy for treatment of various diseases by degrading of disease-related proteins in recent years. Up to now, most PROTAC molecules are mainly aimed at the degradation of intracellular proteins, but many disease-related proteins are membrane or extracellular proteins. The targeted degradation of membrane proteins would be an attractive and general strategy for discovery of novel PROTACs. Herein, we report the development of multi-targeted kinase inhibitor sorafenib-based PROTACs, they can selectively degrade platelet-derived growth factor receptor beta (PDGFR-β). We provide a method that can be used to degrade cell membrane proteins. To our knowledge, this study also is the first report of PROTAC induced PDGFR-β degradation in Cancer cells.

Keywords

Bifunctional molecules; Membrane protein; Multi-targeted inhibitors; PDGFR-β; PROTAC; Protein degradation.

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