ArticleNaunyn-Schmiedeberg's archives of pharmacology2014
Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer.Acta pharmaceutica Sinica. B · 2024Review
- Interleukin-1 receptor-associated kinase 4 (IRAK4) is a critical regulator of inflammatory signalling through toll-like receptors 4 and 7/8 in murine and human lungs.British journal of pharmacology · 2024Article
- Swollen Feet: Considering the Paradoxical Roles of Interleukins in Nephrotic Syndrome.Biomedicines · 2024Review
- Toll-like receptor signalling via IRAK4 affects epithelial integrity and tightness through regulation of junctional tension.Development (Cambridge, England) · 2023Article
- Analysis and therapeutic targeting of the IL-1R pathway in anaplastic large cell lymphoma.Blood · 2023Article
- Renoprotective Effect ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Reno-protective effects of Phosphodiesterase 5 inhibitors.Clinical and experimental nephrology · 2021Review
- Dissecting the Molecular Mechanism of Wang-Bi Capsule in the Treatment of Experimental Rheumatoid Arthritis Based on Synovial Tissue Proteomic Analysis.Journal of immunology research · 2021Article
- Minimizing Ischemia Reperfusion Injury in Xenotransplantation.Frontiers in immunology · 2021Review
- Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma.ACS medicinal chemistry letters · 2020Article
- Therapeutic effects of interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 on diabetic nephropathy in type 2 diabetic mice.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- IRAK4 mediates colitis-induced tumorigenesis and chemoresistance in colorectal cancer.JCI insight · 2019Article
- Irak-4 rs4251481 gene variant: as a risk factor on inflammatory bowel diseaseTurkish journal of medical sciences · 2019Article
- Renoprotective effects of the novel prostaglandin EP4 receptor-selective antagonist ASP7657 in 5/6 nephrectomized chronic kidney disease rats.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats.Acta pharmacologica Sinica · 2018Article
- Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats.Clinical and experimental nephrology · 2018Article
- Tumor-Stroma IL1β-IRAK4 Feedforward Circuitry Drives Tumor Fibrosis, Chemoresistance, and Poor Prognosis in Pancreatic Cancer.Cancer research · 2018Article
- Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
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8 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Renal inflammation is a final common pathway of chronic kidney disease (CKD), and its progression can be used to effectively gauge the degree of renal dysfunction. Interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK-4) has been reported to be a pivotal molecule for IL-1 receptor- and Toll-like receptor-induced signaling and activation of proinflammatory mediators. In this study, we hypothesized that if inflammation plays a key role in renal failure, then the anti-inflammatory effect of IRAK-4 inhibitor should be effective in improving CKD. To determine its pharmacological potency, we investigated the renoprotective properties of the novel IRAK-4 inhibitor AS2444697 (N-[3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-2-(2-methylpyridin-4-yl)-1,3-oxazole-4-carboxamide hydrochloride (1:1)) in 5/6 nephrectomized (Nx) rats, a model of CKD. Six weeks' repeated administration of AS2444697 (0.3-3 mg/kg, twice daily) dose-dependently and significantly reduced urinary protein excretion and prevented the development of glomerulosclerosis and interstitial fibrosis without affecting the blood pressure. In addition, AS2444697 showed beneficial effects on renal function as demonstrated by the decrease in levels of plasma creatinine and blood urea nitrogen and attenuation of decline in creatinine clearance. 5/6 Nx rats exhibited low-grade inflammation as evidenced by increased renal mRNA expression and plasma levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1) and C-reactive protein as a marker of systemic inflammation. AS2444697 significantly reduced or showed a decreasing trend in expression and levels of these inflammatory parameters. These results suggest that AS2444697 suppresses the progression of chronic renal failure via anti-inflammatory action and may therefore be potentially useful in treating CKD patients.
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