ArticleJournal of inherited metabolic disease2015
Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate.
Article in Journal of inherited metabolic disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pilot Clinical Trial to Investigate the Safety and Efficacy of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
A Phase II, Multicentric, Prospective, Non-comparative Clinical Trial to Assess the Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency (PDH) Patients With Glycerol Phenybutyrate (RAVICTI®)
Who cites it
19 citing papers in PubMed, 52 citations in OpenAlex.
- Aerobic glycolysis drives differentiation of unilocular adipocytes.Journal of lipid research · 2026Article
- Pyruvate Dehydrogenase Complex Deficiency: A Review of Treatments and Case Series.International journal of molecular sciences · 2026Review
- Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats.Iranian journal of basic medical sciences · 2025Article
- Sodium Phenylbutyrate Attenuates Cisplatin-Induced Acute Kidney Injury Through Inhibition of Pyruvate Dehydrogenase Kinase 4.Biomedicines · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Phenylbutyrate and Dichloroacetate Enhance the Liquid-Stored Boar Sperm Quality via PDK1 and PDK3.International journal of molecular sciences · 2023Article
- Alpha-Lipoic Acid Protects Against Doxorubicin-Induced Cardiotoxicity by Regulating Pyruvate Dehydrogenase Kinase 4.Cardiovascular toxicology · 2022Article
- Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency.British journal of biomedical science · 2022Review
- Heterogeneous Expression and Subcellular Localization of Pyruvate Dehydrogenase Complex in Prostate Cancer.Frontiers in oncology · 2022Article
- Pt(IV) Prodrugs with NSAIDs as Axial Ligands.International journal of molecular sciences · 2021Review
- Changes in Serum Levels and Gene Expression ofCell journal · 2021Article
- Current progress in the therapeutic options for mitochondrial disorders.Physiological research · 2020Article
- Article
- Real-time hyperpolarizedScientific reports · 2019Article
- Hexokinase II promotes the Warburg effect by phosphorylating alpha subunit of pyruvate dehydrogenase.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2019Article
- Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients.European journal of applied physiology · 2019Article
- Triple action Pt(iv) derivatives of cisplatin: a new class of potent anticancer agents that overcome resistance.Chemical science · 2018Article
- Investigational new drugs for brain cancer.Expert opinion on investigational drugs · 2016Review
- Pyruvate Dehydrogenase Kinases: Therapeutic Targets for Diabetes and Cancers.Diabetes & metabolism journal · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Pyruvate dehydrogenase complex (PDHC) is a key enzyme in metabolism linking glycolysis to tricarboxylic acid cycle and its activity is tightly regulated by phosphorylation catalyzed by four pyruvate dehydrogenase kinase (PDK) isoforms. PDKs are pharmacological targets for several human diseases including cancer, diabetes, obesity, heart failure, and inherited PDHC deficiency. We investigated the inhibitory activity of phenylbutyrate toward PDKs and found that PDK isoforms 1-to-3 are inhibited whereas PDK4 is unaffected. Moreover, docking studies revealed putative binding sites of phenylbutyrate on PDK2 and 3 that are located on different sites compared to dichloroacetate (DCA), a previously known PDK inhibitor. Based on these findings, we showed both in cells and in mice that phenylbutyrate combined to DCA results in greater increase of PDHC activity compared to each drug alone. These results suggest that therapeutic efficacy can be enhanced by combination of drugs increasing PDHC enzyme activity.
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What OpenQuestion holds
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.