2. Academic Validation
  3. Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

  • Future Med Chem. 2024 Apr;16(7):665-677. doi: 10.4155/fmc-2023-0301.
Yanyu Ma 1,  Yidan Song 1,  Junyi Wang 1,  Xiayu Shi 1,  Zhen Yuan 1,  Shuang Li 1,  Honglin Li 1 2 3,  Zhuo Chen 1,  Shiliang Li 1 2
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai, China.
  • 2 Innovation Center for AI & Drug Discovery, East China Normal University, Shanghai, 200062, China.
  • 3 Lingang Laboratory, Shanghai, 200031, China.
PMID: 38390730 DOI: 10.4155/fmc-2023-0301
Abstract

Background: DJ-1 is a ubiquitously expressed protein with multiple functions. Its overexpression has been associated with the occurrence of several cancers, positioning DJ-1 as a promising therapeutic target for Cancer treatment. Methods: To find novel inhibitors of DJ-1, we employed a hybrid virtual screening strategy that combines structure-based and ligand-based virtual screening on a comprehensive compound library. Results: In silico study identified six hit compounds as potential DJ-1 inhibitors that were assessed in vitro at the cellular level. Compound 797780-71-3 exhibited antiproliferation activity in ACHN cells with an IC50 value of 12.18 μM and was able to inhibit the Wnt signaling pathway. This study discovers a novel covalent inhibitor for DJ-1 and paves the way for further optimization.

Keywords

DJ-1; cancer treatment; covalent inhibitor; molecular docking; virtual screening.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-162520
    DJ-1 Inhibitor
    Wnt