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Chemical Research in Chinese Universities

, Volume 34, Issue 2, pp 221–228 | Cite as

Design and Synthesis of Proteolysis Targeting Chimeras for Inducing BRD4 Protein Degradation

  • Shihui Wang
  • Haiyan Li
  • Yue Wang
  • Yang Gao
  • Shanshan Yu
  • Qianqian Zhao
  • Xiangqun Jin
  • Haibin Lu
Article
  • 49 Downloads

Abstract

In this paper, we synthesized a series of proteolysis targeting chimeras(PROTACs) using VHL E3 ligase ligands for BRD4 protein degradation. One of the most promising compound 19g exhibited robust potency of BRD4 inhibition with IC50 value of (18.6±1.3) nmol/L, respectively. Furthermore, compound 19g potently inhibited cell proliferation in BRD4-sensitive cell lines RS4;11 with IC50 value of (34.2±4.3) nmol/L and capable of inducing de-gradation of BRD4 protein at 0.4—0.6 μmol/L in the RS4;11 leukemia cells. These data show that compound 19g is a highly potent and efficacious BRD4 degrader.

Keywords

Proteolysis targeting chimera(PROTAC) BRD4 degrader VHL ligand 

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Copyright information

© Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Shihui Wang
    • 1
  • Haiyan Li
    • 2
  • Yue Wang
    • 1
  • Yang Gao
    • 1
  • Shanshan Yu
    • 1
  • Qianqian Zhao
    • 1
  • Xiangqun Jin
    • 1
  • Haibin Lu
    • 1
  1. 1.College of PharmacyJilin UniversityChangchunP. R. China
  2. 2.Affiliated Hospital of Changchun University of Chinese MedicineChangchunP. R. China

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