Abstract: FR-PO0042
Artificial Intelligence Discovers a Novel Mincle-Specific Inhibitor from Pharmaceutical Formulation for Blocking Macrophage-Driven AKI
Session Information
- AKI: Epidemiology, Risk Factors, and Prevention
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Chung, Yat Fai, The Chinese University of Hong Kong Faculty of Medicine, Hong Kong, Hong Kong
- Tang, Chiu Tsun Philip, The Chinese University of Hong Kong Faculty of Medicine, Hong Kong, Hong Kong
- Nikolic-Paterson, David J., Monash University, Melbourne, Victoria, Australia
- Lan, Hui Y., The Chinese University of Hong Kong Faculty of Medicine, Hong Kong, Hong Kong
- Tang, Sydney, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Tang, Patrick Ming-Kuen, The Chinese University of Hong Kong Faculty of Medicine, Hong Kong, Hong Kong
Background
Acute kidney injury (AKI) is a global health crisis with over 2 million deaths annually, where 10% of the patients will develop into kidney failure. However, there is still lack of effective targeted therapy for AKI and block its potential transition into chronic kidney disease as well as kidney failure in clinic.
Methods
Recently, we identified pattern recognition receptor Mincle as key regulator for the macrophage-driven AKI in mice and further confirmed its clinical relevance in kidney patients with single-cell bioinformatics. However, the lack of Mincle specific inhibitor largely limits the transition of our bench-top discovery into a solution for the unmet clinical need. Encouragingly, by using an artificial intelligence guided drug discovery platform, we successfully identified a single ingredient from a pharmaceutical formulation as novel specific inhibitor for Mincle.
Results
Here, we experimentally confirmed not only its physical binding to the Mincle protein at molecular level, but also its inhibitory effect on the Mincle expression, M1 phenotypes and pro-inflammatory activities on macrophages in vitro and in vivo. More importantly, its mono-treatment effectively alleviates the macrophage-driven renal inflammation, AKI-CKD transition as well as renal failure in the UUO and IRI induced mice.
Conclusion
This novel Mincle specific inhibitor may represent a fully translatable macrophage-targeted therapy for patients with AKI in the clinics.
Acknowledgements
Health and Medical Research Fund (10210726, 11220576), Research Grants Council of Hong Kong (C4013-24G), Passion for Perfection Scheme (PFP202210-004), Faculty Innovation Award (4620528).
AI discovers a novel Mincle specific inhibitor from FDA drugs for AKI therapy.
Funding
- Other NIH Support