ArticleInternational journal of molecular sciences2025
A Novel TLR4 Inhibitor DB03476 Rescued Renal Inflammation in Acute Kidney Injury Model.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Effect of Lactiplantibacillus plantarum SCS6 on pancreatic oxidative damage in mice with type 2 diabetes based on gut-pancreas axis.Antonie van Leeuwenhoek · 2026Article
- Mogroside V Alleviates Renal Injury in Diabetic Mice via Regulation of theInternational journal of molecular sciences · 2026Article
- Factors Modulating Mitochondrial Function after Arterial Injury: Past-to-Present Evidence for the Devising of Future Preventive and Therapeutic Strategies.Journal of cardiovascular translational research · 2026Review
- The role of epigenetic signatures in type 2 diabetes: therapeutic advances and lifestyle interventions.Acta diabetologica · 2026Review
- Inhibition of aerobic glycolysis suppresses ferroptosis via activation of the AMPK-FoxO3a pathway in epileptic rats.Molecular biology reports · 2026Article
- Pharmacological effect of (±)-trans-3-methylfentanyl and (±)-cis-3-methylfentanyl.Psychopharmacology · 2026Article
- Hsa_circ_0002103 promotes progression of colorectal cancer via miR-193a-3p/CCND1 axis.Molecular and cellular biochemistry · 2026Article
- Neferine alleviated corticosterone-induced depressive-like behaviors in mice via the inhibition of TNF/NF-κB pathway by binding to PPARγ.Molecular neurobiology · 2026Article
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Authors and funding
10 authors.
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Abstract
Acute kidney injury (AKI) is a critical clinical syndrome characterized by a rapid decline in renal function, frequently resulting from ischemia, nephrotoxicity, or sepsis. It represents a major global health burden due to its high morbidity and mortality and its strong association with progression to chronic kidney disease. In this study, we identified a novel small-molecule TLR4 inhibitor, DB03476, via structure-based virtual screening targeting the intracellular TIR domain of murine Tlr4. Molecular dynamics simulations confirmed that DB03476 stabilizes Tlr4 without altering its global conformation. In a murine ischemia-reperfusion-induced AKI model, DB03476 administration significantly attenuated renal inflammation, macrophage infiltration, and apoptosis and suppressed the TLR4/MyD88/NF-κB pathway. Moreover, DB03476 exhibited cross-species efficacy by binding conserved residues in human TLR4 with high affinity. Functional validation using human kidney organoids confirmed its protective effects against inflammatory challenge. These results demonstrate DB03476 as a promising therapeutic agent for AKI through selective inhibition of TLR4-mediated inflammatory responses.
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