2. Academic Validation
  3. Identification of fenoldopam as a novel LSD1 inhibitor to abrogate the proliferation of renal cell carcinoma using drug repurposing strategy

Identification of fenoldopam as a novel LSD1 inhibitor to abrogate the proliferation of renal cell carcinoma using drug repurposing strategy

  • Bioorg Chem. 2021 Mar;108:104561. doi: 10.1016/j.bioorg.2020.104561.
Yan Zheng 1,  Yuan Ma 2,  Huixia Cao 1,  Lei Yan 1,  Yue Gu 1,  Xuejing Ren 1,  Xiaojing Jiao 1,  Shengfeng Wan 1,  Fengmin Shao 3
Affiliations

Affiliations

  • 1 Key Laboratory of Immunization of Kidney Disease, People's Hospital of Henan Province, China.
  • 2 Institute of Clinical Medicine, Urodynamic Center and Department of Urology, The First Affiliated Hospital of Zhengzhou University, China.
  • 3 Key Laboratory of Immunization of Kidney Disease, People's Hospital of Henan Province, Zhengzhou University, China. Electronic address: [email protected].
PMID: 33349457 DOI: 10.1016/j.bioorg.2020.104561
Abstract

Although targeted therapy for renal cell carcinoma (RCC) has achieved good therapeutic effects in clinic, a considerable number of patients develop drug resistance over time. So, there is still an urgent need to develop new drugs for RCC treatment. As LSD1 is considered as a promising drug target in diverse cancers, including RCC, we tried to find new LSD1 inhibitor using drug repurposing strategy from a compound library, and fenoldopam, an FDA-approved drug, was identified as a potent LSD1 inhibitor with IC50 = 0.8974 μM in a reversible manner. Molecular docking predicted that fenoldopam occupied the FAD cavity of LSD1, forming hydrogen bonds with surrounding residues. Moreover, fenoldopam inactivated LSD1 and performed antiproliferative activity against ACHN cells and promoted cells Apoptosis in vitro. Taken together, fenoldopam was identified as a novel LSD1 inhibitor firstly, and may serve as a new skeleton for RCC therapy.

Keywords

Cancer treatment; Fenoldopam; LSD1; Renal cell carcinoma.

Figures
Products