2. Academic Validation
  3. Drug repurposing screens to identify potential drugs for chronic kidney disease by targeting prostaglandin E2 receptor

Drug repurposing screens to identify potential drugs for chronic kidney disease by targeting prostaglandin E2 receptor

  • Comput Struct Biotechnol J. 2023 Jul 7:21:3490-3502. doi: 10.1016/j.csbj.2023.07.007.
Hung-Jin Huang 1,  Yu-Hsuan Lee 2,  Li-Chin Sung 3 4 5 6,  Yi-Jie Chen 7,  Yu-Jhe Chiu 7,  Hui-Wen Chiu 6 7 8 9,  Cai-Mei Zheng 1 6 10
Affiliations

Affiliations

  • 1 Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 2 Department of Cosmeceutics, China Medical University, Taichung, Taiwan.
  • 3 Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 4 Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
  • 5 Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.
  • 6 TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.
  • 7 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 8 Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
  • 9 Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University.
  • 10 Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
PMID: 37484490 DOI: 10.1016/j.csbj.2023.07.007
Abstract

Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current therapies only delay disease progression and have limited treatment effects. Hence, the development of innovative therapeutic approaches to mitigate the progression of CKD has become an attractive issue. To date, the incidence of CKD is still increasing, and the biomarkers of the pathophysiologic processes of CKD are not clear. Therefore, the identification of novel therapeutic targets associated with the progression of CKD is an attractive issue. It is a critical necessity to discover new therapeutics as nephroprotective strategies to stop CKD progression. In this research, we focus on targeting a prostaglandin E2 receptor (EP2) as a nephroprotective strategy for the development of additional anti-inflammatory or antifibrotic strategies for CKD. The in silico study identified that ritodrine, dofetilide, dobutamine, and citalopram are highly related to EP2 from the results of chemical database virtual screening. Furthermore, we found that the above four candidate drugs increased the activation of Autophagy in human kidney cells, which also reduced the expression level of fibrosis and NLRP3 inflammasome activation. It is hoped that these findings of the four candidates with anti-NLRP3 inflammasome activation and antifibrotic effects will lead to the development of novel therapies for patients with CKD in the future.

Keywords

Autophagy; Chronic kidney disease; Drug repurposing; Fibrosis; Inflammasome.

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