ArticlePloS one2014
Diisopropylamine dichloroacetate, a novel pyruvate dehydrogenase kinase 4 inhibitor, as a potential therapeutic agent for metabolic disorders and multiorgan failure in severe influenza.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Viral warriors: Unlocking the immune system's potential with oncolytic viruses in cancer immunotherapy.Molecular therapy. Oncology · 2025Review
- Synergistic anti-tumor effect of fenbendazole and diisopropylamine dichloroacetate in immunodeficient BALB/c nude mice transplanted with A549 lung cancer cells.Translational lung cancer research · 2025Article
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level.Scientific reports · 2024Article
- Oncolytic Virotherapy: A New Paradigm in Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Article
- Orchestration of Mitochondrial Function and Remodeling by Post-Translational Modifications Provide Insight into Mechanisms of Viral Infection.Biomolecules · 2023Review
- PDK4 Inhibition Ameliorates Melatonin Therapy by Modulating Cerebral Metabolism and Remyelination in an EAE Demyelinating Mouse Model of Multiple Sclerosis.Frontiers in immunology · 2022Article
- Metabolic Modifications by Common Respiratory Viruses and Their Potential as New Antiviral Targets.Viruses · 2021Review
- The Mechanism behind Influenza Virus Cytokine Storm.Viruses · 2021Review
- Cryptotanshinone, a novel PDK 4 inhibitor, suppresses bladder cancer cell invasiveness via the mTOR/β‑catenin/N‑cadherin axis.International journal of oncology · 2021Article
- Metabolic shifts modulate lung injury caused by infection with H1N1 influenza A virus.Virology · 2021Article
- Targeting inflammatory cytokine storm to fight against COVID-19 associated severe complications.Life sciences · 2021Review
- Factors Associated with Increased Morbidity and Mortality of Obese and Overweight COVID-19 Patients.Biology · 2020Review
- Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice.Scientific reports · 2020Article
- Targeted Metabolic Reprogramming to Improve the Efficacy of Oncolytic Virus Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Bioenergy Crisis in Coronavirus Diseases?Brain sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe influenza is characterized by cytokine storm and multiorgan failure with metabolic energy disorders and vascular hyperpermeability. In the regulation of energy homeostasis, the pyruvate dehydrogenase (PDH) complex plays an important role by catalyzing oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis, and thus its activity is linked to energy homeostasis. The present study tested the effects of diisopropylamine dichloroacetate (DADA), a new PDH kinase 4 (PDK4) inhibitor, in mice with severe influenza. Infection of mice with influenza A PR/8/34(H1N1) virus resulted in marked down-regulation of PDH activity and ATP level, with selective up-regulation of PDK4 in the skeletal muscles, heart, liver and lungs. Oral administration of DADA at 12-h intervals for 14 days starting immediately after infection significantly restored PDH activity and ATP level in various organs, and ameliorated disorders of glucose and lipid metabolism in the blood, together with marked improvement of survival and suppression of cytokine storm, trypsin up-regulation and viral replication. These results indicate that through PDK4 inhibition, DADA effectively suppresses the host metabolic disorder-cytokine cycle, which is closely linked to the influenza virus-cytokine-trypsin cycle, resulting in prevention of multiorgan failure in severe influenza.
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