dichloroacetate topical / Generic mfg. - LARVOL DELTA

Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: (clinicaltrials.gov) - P3 | N=34 | Active, not recruiting | Sponsor: Saol Therapeutics Inc | Trial completion date: Mar 2025 ➔ Aug 2025 | Trial primary completion date: Mar 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Metabolic Disorders

Synergistic and Antagonistic Effects of Metformin-caffeine and Metformin-dichloroacetate Combinations on Cell Viability of Lung Adenocarcinoma Under Hypoxia (ATS 2025) - "These findings suggest that hypoxia is a factor of drug resistance and that the combination of metformin and caffeine could be a complementary therapy in the treatment of lung cancer when hypoxia is not present. However, we consider that additional studies and new proposals are needed to reverse the Warburg phenotype in lung adenocarcinoma cells."

Late-breaking abstract • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pyruvate Fate Is a Determinant of Fibroblast Activation in Lung Fibrosis (ATS 2025) - "PDK1 was inhibited using dichloroacetate (DCA) to assess its impact on mitochondrial respiration and fibroblast activation... These findings highlight the pivotal role of PGK1 in metabolic reprogramming and fibroblast activation in IPF. The non-canonical mitochondrial role of cytosolic PGK1 enhances glycolysis while suppressing mitochondrial respiration via PDH inactivation. Targeting the PGK1-PDK1 axis not only restores mitochondrial function but also reduces collagen production, suggesting a promising therapeutic strategy for IPF that warrants further investigation."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • PGK1

Regulation of Brain Glucose Metabolism in Type 1 Diabetes (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Yale University | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Oct 2025 ➔ May 2026

Enrollment open • Trial completion date • Trial primary completion date • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Mitochondria-targeting natural product rhein conjugated with dichloroacetate as the dual inhibitor of glycolysis and oxidative phosphorylation to off energize cancer cells and induce ROS storm. (PubMed, Theranostics) - "Eventually, the polarization state of tumor-associated macrophages could be effectively reversed following oral administration. This study designed a small-molecule dual-inhibitor of glycolysis and OXPHOS to circumvent metabolic adaptations and simultaneously induce immunogenic cell death for macrophages repolarization, thereby synergistically promoting antitumor efficacy."

Journal • Oncology

Impact of seasonal variations and water quality parameters on the formation of trihalomethanes and haloacetic acids in drinking water treatment processes. (PubMed, J Environ Manage) - "For HAAs, dichloroacetic acid displayed the highest seasonal variability, peaking in autumn at 28 μg/L. These findings highlight the need for seasonally adaptive treatment strategies, particularly during high-risk autumn periods when DBPFP levels are elevated. This study provides actionable insights into optimizing treatment protocols to improve DBP control, emphasizing seasonal adjustments' critical role in ensuring compliance with water quality standards."

Journal

Discovery and Validation of a novel small molecule metabolic inhibitor targeting glioblastoma growth (AACR 2025) - "In vitro assays revealed that the UIC novel inhibitor effectively suppressed U87 cell migration and invasion compared to dichloroacetate (DCA), another PDK1 inhibitor...These findings suggest that the UIC novel inhibitor is a potent inhibitor of PDK1 with significant anti-tumor activity in GBM models, offering a promising therapeutic strategy for targeting metabolic vulnerabilities in GBM. Further clinical evaluation of the UIC novel inhibitor is warranted to explore its potential as a novel treatment option for glioblastoma patients."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • EGFR • PDK1

Targeting PGK1 to enhance ferroptosis in breast cancer (AACR 2025) - "Notably, depletion of PGK1 sensitized TNBC cells to ferroptotic cell death induced by erastin, an activator of ferroptosis, and decreased colony formation and attenuated migratory ability of tumor cells...Furthermore, we demonstrated that the glycolytic inhibitor, sodium dichloroacetate (DCA), enhanced ferroptosis, while the glycolysis inducers such as hypoxia and oligomycin reduced ferroptotic cell death, in the tumor cells subjected to PGK1 depletion...This study demonstrates that PGK1 inhibition can attenuates GPX4, elevate pyruvate dehydrogenase expression, and cause a metabolic shift, thereby sensitizing tumor cells to ferroptosis induction. Thus, PGK1 may be exploited as a therapeutic target for overcoming ferroptosis resistance in breast cancer."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ACSL4 • GPX4 • PGK1 • TFRC

Chemistry Outside the Flask: Redefining Selectivity In Vivo with Image Guidance. (PubMed, ACS Pharmacol Transl Sci) - "We report our experience in a swine model using a strong electrophile, dichloroacetyl chloride, dissolved in a hydrophobic vehicle and delivered to the liver with high spatial selectivity using a microcatheter. Compared with positive controls, very little of the reaction product, dichloroacetate, a known inhibitor of pyruvate dehydrogenase kinase, was detected in plasma over 4 h. We further demonstrated persistence of the material for 24 h with highly localized and well-defined coagulative necrosis in the target vascular bed, without evidence of dose-limiting toxicity over the duration of the experiment."

Journal • Preclinical • Oncology

Expanded Access Treatment Protocol With DCA for Patients With PDCD (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Saol Therapeutics Inc

New trial • Metabolic Disorders

Determination of haloacetic acids in municipal tap water and swimming pool water using portable capillary liquid chromatography - mass spectrometry. (PubMed, J Chromatogr A) - "Dichloroacetic acid (DCAA) was detected in local tap water at the level of 5.3 µg/L, while 142.4 µg/L and 311.4 µg/L of DCAA and trichloroacetic acid (TCAA), respectively, were determined in local swimming pool water. The small-footprint capLC-MS system is compatible with the on-site analysis within water treatment plants and provides a cost-effective and green solution for the quantification of HAA9."

Journal

Exposure to Disinfection By-Products and Risk of Diminished Ovarian Reserve: Case-Control Evidence and Cellular Metabolomic Insights. (PubMed, Reprod Toxicol) - "Serum concentrations of DBPs, including dibromoacetic acid (DBAA), monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), chlorate, and perchlorate, were measured to evaluate DBP exposure...Metabolomics data suggested that DBAA and perchlorate might have contributed to DOR by disrupting arginine biosynthesis and purine metabolism, respectively. In conclusion, DBPs exposure might have contributed to DOR risk by disrupting granulosa cell (GC) metabolism."

Journal • Infectious Disease

Impaired Mitochondrial Oxidative Phosphorylation in Hepatic DNTregs Leads to Reduced Immunoregulatory Function and Exacerbated MASLD Progression (APASL 2025) - "During MASLD progression, the reduced mitochondrial OXPHOS in DNTregs led to a decrease in the mtROS-H3K9/H3K27 acetylation-Prf1/GzmB axis, which in turn impaired the immunoregulatory function of DNTregs and weakened their suppressive effect on MASLD."

Hepatology • Inflammation • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD4 • CD8 • GZMB • HAT1 • NCAM1 • PRF1

Molecular Dynamics Study on the Heat of Phase Transition of Chloroacetate from the Bulk to the Surface Phases. (PubMed, Langmuir) - "Based on the surface adsorption theory developed in our group and molecular dynamics simulations, the adsorption behaviors of methyl chloroacetate, ethyl chloroacetate, propyl chloroacetate, methyl dichloroacetate, and methyl trichloroacetate at the vapor-liquid interface have been thoroughly investigated...Molecular dynamics simulation is exploited to calculate the entropies of these five liquids in the surface and bulk regions at various temperatures. The variation trends of the simulated results are consistent with those of the phase transition heats determined with our surface adsorption theory."

Journal

Removal efficiency and adaptive response mechanisms of microalgal-bacterial granular sludge in treating chloramphenicol-laden wastewater. (PubMed, J Hazard Mater) - "CAP degradation appears to proceed via the amide bond hydrolase EstDL136, thereby reducing its toxicity and producing less harmful byproducts such as 2,2-dichloroacetic acid. This study provides new insights into how CAP affects MBGS communities and identifies the mechanisms for CAP degradation, offering valuable insights that MBGS could serve as an effective and environmentally sustainable technology for the treatment of wastewater containing antibiotic pollutants."

Journal

Non-targeted metabolomic study in plasma in rats with post-traumatic osteoarthritis model. (PubMed, PLoS One) - "Taurocholate, indoleacrylic acid, alpha-ketoglutarate, and isocitric acid may serve as biomarkers for PTOA joint injury in rats. Menadione, adenosine 5'-monophosphate, and Arg-Gly-Asp exhibited differential expression between severe and mild PTOA groups in rats, potentially reflecting the injury's severity. Further investigation into these molecules in human tissues is warranted to ascertain their utility as biomarkers for PTOA in humans."

Biomarker • Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology

Seasonal Variations in Potable Water Quality of Bahawalpur City: A Comprehensive Assessment of Major Ions, Organic Matter, and Disinfection Byproducts. (PubMed, Environ Monit Assess) - "Dichloroacetic acid exceeded the WHO permissible limits in 33% and 11% of samples during summer and winter, respectively...This study provides valuable information to achieve Sustainable Development Goal 6 which is for clean water and sanitation. So, this research can provide significant data to the policy makers to improve the water quality in developing countries like Pakistan."

Journal

Optimization of anode positioning in constructed wetlands coupled with microbial fuel cells based on C/O microenvironment for simultaneous removal of disinfection by-products and nitrogen. (PubMed, J Hazard Mater) - "It was observed that the CW-MFC with the anode positioned centrally exhibited considerable nitrogen removal (TN removal efficiency: 56.3 ± 8.6 %) and HAAs degradation performance (dichloroacetic acid removal efficiency: 97.8 ± 1.3 %)...Key genes (HAAs and carbon-nitrogen metabolic) were upregulated, clarifying the mechanisms of synergistic removal of HAAs and nitrogen in CW-MFCs with centrally positioned anodes. This study highlights the importance of CW-MFCs with anode positioning in the synergistic removal of DBPs and nitrogen, providing straightforward and feasible strategy for optimizing CW-MFC performance and scaling up."

Journal

Urinary biomarkers of drinking water disinfection byproducts in relation to blood-based liver function parameters among reproductive-aged Chinese women. (PubMed, Sci Total Environ) - "DCAA but not TCAA exposure may contribute to damaged liver function in reproductive-aged women."

Biomarker • Journal • Hepatology

Targeting the PDK/PDH axis modulates neutrophil and smooth muscle cell pathological responses and prevents abdominal aortic aneurysm formation. (PubMed, Cardiovasc Res) - "We show that the PDK/PDH axis is skewed in human AAA. Through the inhibition of PDK, in vitro and in vivo, we demonstrated that the PDK/PDH axis is a key regulator of vascular- and neutrophil-associated pathological responses with AAA formation. Our study pinpoints immunometabolic reprogramming using PDK inhibitors as an attractive strategy to fight AAA disease."

Journal • Cardiovascular • Inflammation • ELANE

Effect and mechanism of Dichloroacetate in the treatment of stroke and the resolution strategy for side effect. (PubMed, Eur J Med Res) - "We describe the causes and solutions of peripheral neuropathy caused by DCA. In summary, this study analyzes the neuroprotective mechanism of DCA in ischemic stroke and the contradiction of the different research results, and discusses the causes and solutions of its adverse effects."

Adverse events • Journal • Review • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Inflammation • Ischemic stroke • Metabolic Disorders • Pain

PDK2-enhanced glycolysis aggravates fibrosis via IL11 signaling pathway in Graves' orbitopathy. (PubMed, Front Immunol) - "In vitro experiments showed successful induction of fibrosis of patient-derived orbital fat/connective tissues, which could be alleviated by dichloroacetic acid (DCA)...In vivo experiment confirmed anti-fibrotic effect of inhibition of glycolysis. PDK2-enhanced glycolysis exacerbates fibrosis via IL11-IL11Rα signaling pathway, shedding light on a potential therapeutic role of metabolic modulators such as DCA in GO treatment."

Journal • Fibrosis • Immunology • Thyroid Eye Disease • Transplantation

Harnessing organic electrolyte for non-corrosive and wide-temperature Na-Cl2 battery. (PubMed, Nat Commun) - "Here we show a non-corrosive ester (methyl dichloroacetate) as a promising alternative to SOCl2, which can form a non-corrosive electrolyte with aluminum chloride and sodium bis(fluorosulfonyl)imide for high-performance rechargeable Na-Cl2 batteries...The electrochemical performance and safety have been further extended to fibre batteries, which realize wearable applications of rechargeable Na-Cl2 batteries. Based on donor number and charge transfer as two key descriptors, we further propose the design principle of organic electrolytes for rechargeable Na-Cl2 batteries, which can fully unlock the designability and sustainability of organic solvents towards practical Na-Cl2 batteries."

Journal

Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: University of Florida | Trial completion date: Jun 2025 ➔ Aug 2026 | Trial primary completion date: Jun 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Lactoferrin-Encapsulated Dichloroacetophenone (DAP) nanoparticles enhance drug delivery and anti-tumor efficacy in prostate cancer. (PubMed, Cancer Lett) - "In this study we demonstrated that DAP exhibited a superior ability to inhibit prostate cancer cell proliferation, migration and colony formation at a lower concentration (20 μM) compared to a previously established inhibitor, dichloroacetate (DCA), which required concentrations of 30 mM or higher. Moreover, lactoferrin-conjugated DAP nanoparticles suppressed the viability of docetaxel-resistant cells exhibiting a higher inhibitory efficacy compared to free DAP and DCA. Targeting PDK1 through lactoferrin-conjugated DAP nanoparticles represents a potent targeted therapeutic strategy for disrupting prostate tumor metabolism and offers promising implications for overcoming drug resistance."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CASP3 • CASP7