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

作者：Ma, Yanyu; Song, Yidan; Wang, Junyi; Shi, Xiayu; Yuan, Zhen; Li, Shuang; Li, Honglin; Chen, Zhuo^*; Li, Shiliang

来源：Future Medicinal Chemistry, 2024.

DOI：10.4155/fmc-2023-0301

• cancer treatment
• covalent inhibitor
• DJ-1
• molecular docking
• virtual screening

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 mu M 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.

• 单位
  华东理工大学