ArticleBritish journal of pharmacology2016
A novel plasminogen activator inhibitor-1 inhibitor, TM5441, protects against high-fat diet-induced obesity and adipocyte injury in mice.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Serpine1 as a potential therapeutic target in pyrrolidine alkaloids-induced hepatic sinusoidal obstruction syndrome.JHEP reports : innovation in hepatology · 2026Article
- Role of the Plasminogen Activation System in Liver Injury and Repair: Knowns and Known Unknowns.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- PAI-1 Inhibitor TM5441 Attenuates Emphysema and Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease.International journal of molecular sciences · 2025Article
- Plasminogen Activation Inhibitor-1 Promotes Resilience to Acute Oxidative Stress in Cerebral Arteries from Females.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Chemical Adjustment of Fibrinolysis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1.Frontiers in immunology · 2024Article
- Macrophage and Adipocyte Mitochondrial Dysfunction in Obesity-Induced Metabolic Diseases.The world journal of men's health · 2021Review
- Inhibition of PAI-1 Promotes Lipolysis and Enhances Weight Loss in Obese Mice.Obesity (Silver Spring, Md.) · 2021Article
- Structural Insight into the Two-Step Mechanism of PAI-1 Inhibition by Small Molecule TM5484.International journal of molecular sciences · 2021Article
- Role of PAI-1 in hepatic steatosis and dyslipidemia.Scientific reports · 2021Observational
- Drug Targeting of Plasminogen Activator Inhibitor-1 Inhibits Metabolic Dysfunction and Atherosclerosis in a Murine Model of Metabolic Syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- The road ahead for health and lifespan interventions.Ageing research reviews · 2020Review
- Unbiased proteomics identifies plasminogen activator inhibitor-1 as a negative regulator of endothelial nitric oxide synthase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Inhibition of Plasminogen Activator Inhibitor-1 Activation Suppresses High Fat Diet-Induced Weight GainFrontiers in pharmacology · 2020Article
- Impaired Peroxisomal Fitness in Obese Mice, a Vicious Cycle Exacerbating Adipocyte DysfunctionAntioxidants & redox signaling · 2019Article
- Dual-reporter high-throughput screen for small-moleculeThe Journal of biological chemistry · 2019Article
- Proteolysis is the most fundamental property of malignancy and its inhibition may be used therapeutically (Review).International journal of molecular medicine · 2019Review
- Inhibition of Plasminogen Activator Inhibitor 1 Attenuates Hepatic Steatosis but Does Not Prevent Progressive Nonalcoholic Steatohepatitis in Mice.Hepatology communications · 2018Article
- Stress granules counteract senescence by sequestration of PAI-1.EMBO reports · 2018Article
- TM5441, a plasminogen activator inhibitor-1 inhibitor, protects against high fat diet-induced non-alcoholic fatty liver disease.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeObesity is one of the most prevalent chronic diseases worldwide, and dysregulated adipocyte function plays an important role in obesity-associated metabolic disorder. The level of plasma plasminogen activator inhibitor-1 (PAI-1) is increased in obese subjects, and PAI-1 null mice show improved insulin sensitivity when subjected to high-fat and high-sucrose diet-induced metabolic stress, suggesting that a best-in-class PAI-1 inhibitor may become a novel therapeutic agent for obesity-associated metabolic syndrome. TM5441 is a novel orally active PAI-1 inhibitor that does not cause bleeding episodes. Hence, in the present study we examined the preventive effect of TM5441 on high-fat diet (HFD)-induced adipocyte dysfunction. EXPERIMENTAL APPROACH: Ten-week-old C57BL/6J mice were fed a normal diet (18% of total calories from fat) or HFD (60% of total calories from fat) for 10 weeks, and TM5441 (20 mg·kg(-1) oral gavage) was administered daily with the initiation of HFD. KEY
resultsTM5441 prevented HFD-induced body weight gain and systemic insulin resistance. TM5441 normalized HFD-induced dysregulated JNK and Akt phosphorylation, suggesting that it prevents the insulin resistance of adipocytes. TM5441 also attenuated the macrophage infiltration and increased expression of pro-inflammatory cytokines, such as inducible nitric oxide synthase, induced by the HFD. In addition, TM5441 prevented the HFD-induced down-regulation of genes involved in mitochondrial biogenesis and function, suggesting that it may prevent adipocyte inflammation and dysregulation by maintaining mitochondrial fitness. CONCLUSION AND IMPLICATIONS: Our data suggest that TM5441 may become a novel therapeutic agent for obesity and obesity-related metabolic disorders.
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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.