dichloroacetate topical / Generic mfg. - LARVOL DELTA

Mitochondria-targeting iridium(III) complex enhances anticancer activity via PDK inhibition and energy metabolism disruption. (PubMed, J Inorg Biochem) - "Here, complex Ir-DCA was developed via the conjugation of the pyruvate dehydrogenase kinases (PDK) inhibitor dichloroacetate (DCA) to an iridium(III) scaffold, to achieve concurrent inhibition of mitochondrial glycolysis and OXPHOS...These events collectively suppress both glycolysis and glucose oxidation, block adenosine triphosphate (ATP) and lactate production, ultimately triggers the caspase-dependent apoptotic cell death pathway. This work validates the efficacy of DCA-functionalized metal complex for dual energy pathway inhibition and emphasizes the translational potential of metabolism reprogramming strategies in cancer therapy."

Journal • Cervical Cancer • Metabolic Disorders • Oncology • Solid Tumor

Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice. (PubMed, Arterioscler Thromb Vasc Biol) - "Conversely, EC-Pdk4-knockdown or pharmacological inhibition with dichloroacetate attenuated TAD progression, preserved vascular integrity, and improved survival. Our findings demonstrate that the pathological EndoMT program is activated in ECs by PDK4, which aggravates TAD development in β-aminopropionitrile-induced mouse models, highlighting PDK4 as a promising therapeutic target for TAD."

Journal • Preclinical • Cardiovascular • Developmental Disorders • PDK4 • SNAI1

Dichloroacetate reprograms metabolism and disrupts ROS adaptation, attenuating stemness to reverse chemoresistance in ovarian cancer (AACR 2026) - "In this study, we investigated the therapeutic potential of Dichloroacetate (DCA), a pan-pyruvate dehydrogenase kinase (PDK) inhibitor, as a strategy to overcome Cisplatin (CP) resistance. Crucially, DCA treatment disrupted this ROS adaptation, inducing a lethal accumulation of ROS specifically in the resistant cells. Collectively, our findings indicate that DCA restores CP sensitivity by targeting ROS metabolism and inhibiting stemness, suggesting it is a promising therapeutic candidate for treating refractory ovarian cancer."

Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

Inhibition of extracellular matrix remodeling and metastatic activity by dichloroacetate and chloroquine in the presence of arsenite in 4nqo-induced oral squamous cell carcinoma (AACR 2026) - "Altogether, our findings show that our combined treatment was able to reprogram the inflammatory process of tumor progression by inhibiting the molecular processes involved in extracellular matrix remodeling and invasion. This combined treatment represents a novel avenue for metabolic-inflammation-targeting strategy for OSCC in particular in view of the limited treatment options and the risk of chemoresistance."

Metastases • Oncology • Oral Cancer • Squamous Cell Carcinoma • MMP9 • TNFA

Neonatal Hyperoxia Induces Metabolic Reprogramming in Senescent Alveolar Macrophages, Leading to Persistent Lung Injury. (PubMed, Front Biosci (Landmark Ed)) - "Neonatal hyperoxia drives the emergence of a heterogeneous population of senescent macrophages characterized by metabolic reprogramming and dysregulated signaling pathways, which contribute to the development and persistence of lung injury."

Journal • Ataxia • Bronchopulmonary Dysplasia • Immunology • Inflammation • Movement Disorders • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • mTOR

DADA Enhances CD8+ T Cell Stemness to Improve Anti-Tumor Immunity and Immunotherapy Efficacy. (PubMed, Adv Sci (Weinh)) - "Here, it is demonstrated that diisopropylamine dichloroacetate (DADA) facilitates CD8+ T cell-mediated anti-tumor immunity and promotes Tpex cells accumulation in the tumor microenvironment...Furthermore, the in vitro expansion of chimeric antigen receptor (CAR)-T cells supplemented with DADA confers them with stemness characteristics, contributing to improved anti-tumor efficacy. Collectively, this study illustrates how DADA-mediated metabolic reprogramming in CD8+ T cell enhances their stemness, underscoring its potential for anti-tumor therapy."

Journal • Oncology

In vitro modeling of nutritional and mitochondria-targeted therapies for osteosarcoma. (PubMed, bioRxiv) - "Current therapies are non-specific, involving primary tumor resection with DNA-damaging chemotherapies like methotrexate, doxorubicin, and cisplatin...We investigated the therapeutic potential in human osteosarcoma primary and metastatic cell lines of metabolic modulating drugs including metformin, cycloheximide, mitochondrial ETC inhibitors (antimycin A, metformin), dichloroacetate, and imipridones (ONC201, ONC206) on mitochondrial function and cell viability, individually and combined under various nutrient conditions across our lines...RNA-Seq transcriptome analysis revealed that effective nutrient and metabolic drug treatments triggered widespread regulatory changes in osteosarcoma cells involving increased translation/splicing with decreased mitochondrial processes such as cholesterol biosynthesis. These results demonstrate the utility of developing combined metabolic and chemotherapeutic treatments for osteosarcoma."

Journal • Preclinical • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

mTOR-driven autophagy suppression defines metabolic vulnerability in CDK4/6 inhibitor-resistant HR+/HER2- breast cancer. (PubMed, Cell Death Dis) - "Using HR+/HER2- BC models with acquired resistance to the CDK4/6 inhibitors Palbociclib or Ribociclib, we uncovered a metabolic vulnerability in highly resistant clones, mediated by mTORC1 hyperactivation and autophagy suppression. Gene expression profiling revealed enrichment of glycolysis and mTORC1 pathways in CDK4/6i-resistant cells, which manifested as heightened sensitivity to the metabolic inhibitors Metformin and Dichloroacetate (DCA)...Clinically, immunohistochemical analysis of a BC cohort revealed a significant correlation between mTORC1 activity (p4E-BP1T37/46) and autophagy suppression (p62 accumulation), supporting the translational relevance of this axis. Our findings propose mTORC1-mediated autophagy defects as a biomarker for metabolic vulnerability in CDK4/6i-resistant BC, offering a rationale for targeting these tumors with metabolic therapies to overcome resistance."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

MPTP and rotenone cause dopaminergic neuronal death by increasing DDIT4 promoter lactylation. (PubMed, Acta Pharmacol Sin) - "A pharmacological reduction in lactate production or inhibition of lactylation with sodium dichloroacetate (DCA) suppressed DDIT4 promoter lactylation and expression, reduced MPP+- and rotenone-induced cell death in SH-SY5Y cells in vitro and partially protected against MPTP-induced TH-positive DA neuron loss in the brains of MPTP-treated mice in vivo...These results provide the first evidence that environmental toxicity-induced metabolic alterations drive histone lactylation of the DDIT4 promoter, directly linking a known PD stress effector gene to a lactate-epigenetic signal underlying DA neuron loss. This study reveals a lactate-epigenetic axis that contributes to environmental toxicant-induced Parkinsonism and identifies lactate metabolism and histone lactylation as promising targets for further preclinical investigation."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • DDIT4

USP30 senses serine/glycine levels to regulate serine biosynthesis and colorectal tumorigenesis by deubiquitinating FTO. (PubMed, Cell Death Differ) - "Furthermore, we identify sodium 2, 2-dichloroacetate (DCA) as a novel inhibitor of USP30, and DCA inhibits CRC serine synthesis and tumor growth. Clinically, USP30, FTO, PHGDH, and PSAT1 levels are highly correlated in CRC tissues. This study provides mechanistic insights into how USP30 senses serine/glycine levels to regulate serine synthesis via the FTO-PHGDH/PSAT1 axis, offering a potential therapeutic strategy for targeting serine/glycine metabolism in cancer."

Journal • Colorectal Cancer • Genetic Disorders • Obesity • Oncology • Solid Tumor • Targeted Protein Degradation • FTO • GPX4 • PARP1 • PHGDH • PSAT1 • SLC7A11 • YTHDF2

Proteomics landscape of early T-cell precursor acute lymphoblastic leukemia reveals deficient oxidative phosphorylation signatures. (PubMed, Cell Rep Med) - "Furthermore, we identify CD109 as an attractive immunophenotypic marker that not only distinguishes ETP-ALL from other hematologic malignancies but also defines a subset with enhanced ETC suppression and heightened metabolic vulnerability to dichloroacetate. These findings elucidate the mechanistic basis of mitochondrial dysregulation in ETP-ALL pathogenesis and nominate CD109 as a promising biomarker for targeted therapeutic strategies."

Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology

Control of algal-derived disinfection by-products with a composite coagulant: Insights into the mechanism from a molecular perspective. (PubMed, Water Res) - "DBPs formation characteristics revealed that trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) precursors were primarily low molecular weight (MW) substances, whereas high-MW components in IOM tended to form trichloromethane (TCM) and dichloroacetonitrile (DCAN)...Additionally, PFTS could efficiently remove N-containing organic precursors such as proteins and peptides, thereby reducing the generation of N-DBPs. The findings of this work will provide a theoretical reference for ensuring summer water supply safety."

Journal

Post-translational modifications of triosephosphate isomerase reveal metabolic vulnerabilities in T-ALL. Effect of combining dichloroacetic acid and the PPI rabeprazole. (PubMed, Biochem J) - "Finally, combined dichloroacetate-rabeprazole treatment induced extensive apoptotic death in Jurkat cells while sparing normal lymphocytes. These findings identify post-translational modifications-bearing TPI isoforms as selective metabolic vulnerabilities in Jurkat cells and support the potential repurposing of thiol-modifying agents, particularly, rabeprazole, as targeted antileukemic strategies."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Effect of Treatment with a Combination of Dichloroacetate and Valproic Acid on Adult Glioblastoma Patient-Derived Primary Cells Xenografts on the Chick Embryo Chorioallantoic Membrane. (PubMed, Pharmaceutics) - "This study aimed to investigate the effectiveness of sodium dichloroacetate (NaDCA) and a sodium valproate NaDCA combination (NaVPA-NaDCA) on formed patients' primary cell tumors on the chick embryo chorioallantoic membrane (CAM). The treatment with NaVPA-NaDCA significantly reduced the expression of PCNA, p53, EZH2 and vimentin in the tested tumors. Data demonstrated an antitumor effect of NaVPA-NaDCA in an in vivo model of a patient's primary glioblastoma cells."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EZH2 • FAP • GFAP • PCNA • TP53 • VIM

Synergistic therapeutic impact of dichloroacetate nanoparticles and doxorubicin in modulating pyruvate dehydrogenase kinase in breast carcinoma model. (PubMed, Sci Rep) - "Dox/DCA-PNPs treatment decreased tumor profile and hepatorenal alterations with PDKs gene suppression, increased cancer cell apoptosis and cycle arrest at G0/G1 phase (76.1 and 64.8%). Dox/DCA-PNPs demonstrated anti-tumor activity via inhibiting PDK enzyme."

Journal • Breast Cancer • Oncology • Solid Tumor

A Multi-Center Retrospective Chart Analysis Identifying Clinical, Biochemical, and Radiographic Signatures of Short-Chain Enoyl-CoA Hydratase (ECHS1) Deficiency (ACMG 2026) - "This study represents the single largest collection of unreported patients and the first manuscript synthesizing all previously reported cases of individuals with ECSH1D, encompassing 113 patients. Overall survival was 77% in our newly reported cohort (N=26) compared with 69% in previously reported patients (N=87). Moreover, we report a 37.5% survival rate in newly reported neonatal onset patients compared with 18.2% in prior reports, possibly reflective of earlier recognition of ECHS1D and greater utilization of therapies including N-acetylcysteine, sodium dichloroacetate, and valine-restriction diet."

Retrospective data • Cardiomyopathy • Cardiovascular • Cerebral Palsy • CNS Disorders • Developmental Disorders • Dystonia • Epilepsy • Metabolic Disorders • Movement Disorders

FDCA Attenuates Neuronal Ferroptosis and Reduces Hemorrhagic Transformation After Ischemic Stroke with High Glucose. (PubMed, Cell Mol Neurobiol) - "The compound fasudil dichloroacetate (FDCA), synthesized with ROCK inhibitor fasudil (F) and PDK inhibitor dichloroacetate (DCA) was previously reported to exhibit neuroprotective effects in ischemic stroke, but whether FDCA could ameliorate HT post-stroke remains unknown. Additionally, FDCA attenuated RSL3-induced neuronal ferroptosis in SH-SY5Y cells in vitro. These results suggest that FDCA holds promise as a potential therapeutic agent for the clinical treatment of HT following ischemic stroke."

Journal • Cardiovascular • Diabetes • Hematological Disorders • Ischemic stroke • ACSL4 • GPX4

Metabolomic profiling reveals alterations in Candida pathophysiology and host interactions during primary oral candidiasis and following antifungal treatment. (PubMed, Sci Rep) - "Antifungal metabolites, specifically dichloroacetate, 1-monopalmitin, and undecane-2-one, were significantly upregulated in the OT group; conversely, fatty acids (palmitic amide, linoleamide, stearamide, and pentadecanal) were downregulated...Our results demonstrate that oral candidiasis is associated with distinct metabolomic alterations compared with healthy controls, and that antifungal therapy reshapes the oral metabolic profiles via complex host-microbiome-fungal metabolic pathways. The identification of oral candidiasis-associated metabolites also highlights their potential as non-invasive biomarkers and therapeutic targets for oral healthcare."

Journal • Candidiasis • Dental Disorders • Immune Modulation • Immunology • Inflammation • Oncology • Xerostomia

lncRNA NKILA Promotes Warburg Effect and Immune Escape in Intrahepatic Cholangiocarcinoma by Regulating the MTX1/TOMM40 Axis. (PubMed, Mediators Inflamm) - "NKILA facilitated proliferation, invasion, Warburg effects, and autophagy of ICC cells by regulating mammalian target of rapamycin (mTOR) pathway, PD-L1 expression, and CD8+ T cytotoxicity, while dichloroacetate (DCA) could reverse these effects...NKILA silencing could inactivate MTX1/TOMM40 axis to inhibit Warburg effect and autophagy-associated immune escape. LncRNA NKILA promotes Warburg effect and immune escape in ICC by regulating the MTX1/TOMM40 axis."

IO biomarker • Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • Transplantation • CD8

Associations between urinary biomarkers of drinking-water disinfection byproducts and fasting plasma glucose: results from the TREE study. (PubMed, J Endocrinol Invest) - No abstract available

Biomarker • Journal • Diabetes

Sepsis and the Liver. (PubMed, Diseases) - "Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI."

Journal • Review • Cholestasis • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • Metabolic Disorders • Septic Shock • Transplantation • NLRP3 • PPARA

Spatial monitoring and analysis of haloacetic acids in drinking water using GIS: a case study of Jamia Nagar, New Delhi. (PubMed, Environ Monit Assess) - "This study investigates the occurrence and spatial variation of five HAA species (monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), monobromoacetic acid (MBAA), and dibromoacetic acid (DBAA)) in drinking water samples collected from eight locations in Jamia Nagar, New Delhi, during March-April 2023...Spatial mapping using kriging interpolation demonstrated higher HAA concentrations at sampling locations farther from the water treatment plant, indicating the effect of longer contact time between chlorine and organic precursors. The results highlight the need to consider HAAs in Indian drinking water standards and suggest that spatial monitoring can guide treatment upgrades and evidence-based policy making to ensure safe drinking water."

Journal

Histone lactylation-mediated up-regulation of IGF2BP2 enhances ferroptosis resistance via Nrf2 in colorectal cancer. (PubMed, Clin Transl Med) - "Lactate drives H3K18la-mediated transcriptional activation of IGF2BP2 in CRC. IGF2BP2 protein stabilises Nrf2 mRNA by binding to its m6A modification site. The lactate-IGF2BP2-Nrf2 axis confers ferroptosis resistance in CRC cells. This pathway simultaneously promotes M2 macrophage polarisation in the tumour microenvironment."

Journal • Colorectal Cancer • Oncology • Solid Tumor • EP300 • IGF2BP2 • IL10 • IL12A • IL1B

Multi-omics integration uncovers metabolic control of H3K27ac in bovine inner cell masses†. (PubMed, Biol Reprod) - "This investigation explores the link between pyruvate metabolism and epigenetic regulation by culturing bovine embryos from day 5 in the presence of sodium dichloroacetate (DCA), an organic acid that enhances the conversion of pyruvate to acetyl-CoA, and sodium iodoacetate (IA), which inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to the inhibition of glycolysis...DCA led to a more robust association with biological processes related to lipid metabolism, while IA presented a higher binding activity linked to processes such as apoptosis and catabolism. The results discussed here corroborate previous evidence of the relationship between energy metabolism and epigenetic reprogramming in pre-implantation bovine embryos, pointing to H3K27ac as an important mark for the immediate response of embryos to environmental changes in culture systems."

Journal • Metabolic Disorders • GAPDH

Positive feedback between histone H4K16 lactylation and glycolysis promotes MAFLD progression. (PubMed, Hepatol Int) - "We identify a lactate-H4K16la-PDK4 axis that drives metabolic reprogramming and MAFLD progression. Targeting PDK4 may represent a therapeutic strategy for MAFLD/MASH."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • PDK4