ArticleJournal of clinical pharmacology2012
Human polymorphisms in the glutathione transferase zeta 1/maleylacetoacetate isomerase gene influence the toxicokinetics of dichloroacetate.
Article in Journal of clinical pharmacology, 2012. 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 27 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.
Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM)
Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Phase III trial of sodium dichloroacetate for pyruvate dehydrogenase complex deficiency in children.JCI insight · 2026Trial
- Trial
- Model Informed Dose Optimization of Dichloroacetate for the Treatment of Congenital Lactic Acidosis in Children.Journal of clinical pharmacology · 2018Trial
- Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans.Drug metabolism and personalized therapy · 2015Trial
- Haplotype variations in glutathione transferase zeta 1 influence the kinetics and dynamics of chronic dichloroacetate in children.Journal of clinical pharmacology · 2015Trial
- Pyruvate Dehydrogenase Complex Deficiency: A Review of Treatments and Case Series.International journal of molecular sciences · 2026Review
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases.International journal of nanomedicine · 2023Review
- Glutathione S-transferase Omega 2 DD genotype is associated with an increased risk of sporadic amyotrophic lateral sclerosis in Chinese men.The Journal of international medical research · 2021Article
- Exposure of Rats to Multiple Oral Doses of Dichloroacetate Results in Upregulation of Hepatic Glutathione Transferases and NAD(P)H Dehydrogenase [Quinone] 1.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Effects of Multiple Doses of Dichloroacetate on GSTZ1 Expression and Activity in Liver and Extrahepatic Tissues of Young and Adult Rats.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Gender-Related Effect of Sodium Dichloroacetate on the Number of Hassall's Corpuscles and RNA NKCC1 Expression in Rat Thymus.BioMed research international · 2019Article
- Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.Pharmacology & therapeutics · 2017Review
- Pharmacogenetic considerations with dichloroacetate dosing.Pharmacogenomics · 2016Review
- Clinically relevant genetic variants of drug-metabolizing enzyme and transporter genes detected in Thai children and adolescents with autism spectrum disorder.Neuropsychiatric disease and treatment · 2016Article
- A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors.Investigational new drugs · 2015Article
- The influence of human GSTZ1 gene haplotype variations on GSTZ1 expression.Pharmacogenetics and genomics · 2015Article
- Investigational cancer drugs targeting cell metabolism in clinical development.Expert opinion on investigational drugs · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Dichloroacetate (DCA), a chemical relevant to environmental science and allopathic medicine, is dehalogenated by the bifunctional enzyme glutathione transferase zeta (GSTz1)/maleylacetoacetate isomerase (MAAI), the penultimate enzyme in the phenylalanine/tyrosine catabolic pathway. The authors postulated that polymorphisms in GSTz1/MAAI modify the toxicokinetics of DCA. GSTz1/MAAI haplotype significantly affected the kinetics and biotransformation of 1,2-¹³C-DCA when it was administered at either environmentally (µg/kg/d) or clinically (mg/kg/d) relevant doses. GSTz1/MAAI haplotype also influenced the urinary accumulation of potentially toxic tyrosine metabolites. Atomic modeling revealed that GSTz1/MAAI variants associated with the slowest rates of DCA metabolism induced structural changes in the enzyme homodimer, predicting protein instability or abnormal protein-protein interactions. Knowledge of the GSTz1/MAAI haplotype can be used prospectively to identify individuals at potential risk of DCA's adverse side effects from environmental or clinical exposure or who may exhibit aberrant amino acid metabolism in response to dietary protein.
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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.