ArticleThe Journal of clinical investigation2018
ASK1 contributes to fibrosis and dysfunction in models of kidney disease.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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The trial behind it
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Who cites it
75 citing papers in PubMed, 137 citations in OpenAlex.
- Plasma proteome signatures of ASK1 inhibition by selonsertib associate with efficacy in the MOSAIC randomized trial for diabetic kidney disease.BMC nephrology · 2025Trial
- Pharmacokinetics, Safety, and Tolerability of Selonsertib, an Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitor, Following First-in-Human Single and Multiple Ascending Doses in Healthy Subjects.Clinical pharmacokinetics · 2020Trial
- Effects of Selonsertib in Patients with Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2019Trial
- Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.Nature reviews. Nephrology · 2026Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- [Research progress on the pathogenesis and clinical treatment of cirrhotic cardiomyopathy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cellular senescence of renal tubular epithelial cells in diabetic kidney disease: emerging mechanisms and targeted interventions.Frontiers in cell and developmental biology · 2026Review
- Lead-Induced Nephrotoxicity and Its Therapeutic Interventions: An Updated Review.Biological trace element research · 2026Review
- Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.Molecular and cellular biochemistry · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- ASK1 limits kidney glucose reabsorption, growth, and mid-late proximal tubule KIM-1 induction when diabetes and Western diet are combined with SGLT2 inhibition.American journal of physiology. Renal physiology · 2025Article
- Comprehending the Role of Metabolic and Hemodynamic Factors Alongside Different Signaling Pathways in the Pathogenesis of Diabetic Nephropathy.International journal of molecular sciences · 2025Review
- Discussion on the treatment of diabetic kidney disease based on the "gut-fat-kidney" axis.International urology and nephrology · 2025Review
- PGAM5 Modulates Macrophage Polarization, Aggravating Inflammation in COPD via the NF-κB Pathway.International journal of chronic obstructive pulmonary disease · 2025Article
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models.Animal models and experimental medicine · 2025Article
- A new Jun amino-terminal kinase inhibitor, KRev-202, inhibits rat ischemic acute injury and the progression to renal fibrosis.Frontiers in pharmacology · 2025Article
- Selonsertib in Patients with Diabetic Kidney Disease: A Phase 2b Randomized Active Run-In Clinical Trial.Journal of the American Society of Nephrology : JASN · 2024Article
- Synthesis and biological evaluation of quinoxaline derivatives as ASK1 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.Cell metabolism · 2024Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress is an underlying component of acute and chronic kidney disease. Apoptosis signal-regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase kinases, and induces apoptotic, inflammatory, and fibrotic signaling in settings of oxidative stress. We describe the discovery and characterization of a potent and selective small-molecule inhibitor of ASK1, GS-444217, and demonstrate the therapeutic potential of ASK1 inhibition to reduce kidney injury and fibrosis. Activation of the ASK1 pathway in glomerular and tubular compartments was confirmed in renal biopsies from patients with diabetic kidney disease (DKD) and was decreased by GS-444217 in several rodent models of kidney injury and fibrosis that collectively represented the hallmarks of DKD pathology. Treatment with GS-444217 reduced progressive inflammation and fibrosis in the kidney and halted glomerular filtration rate decline. Combination of GS-444217 with enalapril, an angiotensin-converting enzyme inhibitor, led to a greater reduction in proteinuria and regression of glomerulosclerosis. These results identify ASK1 as an important target for renal disease and support the clinical development of an ASK1 inhibitor for the treatment of DKD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.