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

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 ad-ditional 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 in-flammasome activation. It is hoped that these findings of the four candidates with anti-NLRP3 inflamma-some activation and antifibrotic effects will lead to the development of novel therapies for patients with CKD in the future.& COPY; 2023 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Automated summary

Renal inflammation and fibrosis are correlated with kidney function deterioration and CKD. Current therapies have limited effects, so innovative approaches are needed to mitigate CKD progression.