dichloroacetate topical / Generic mfg. - LARVOL DELTA

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."

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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."

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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

N-acetylcysteine induced lactate reprogramming is a targetable metabolic susceptibility in glioblastoma. (SNO 2025) - "To test the effects of lowering lactate levels on NAC-induced cytotoxicity, we treated glioma cells with the mitochondrial pyruvate dehydrogenase enzyme complex inhibitor dichloroacetate (DCA)...Blocking lactate import/export via inhibition of MCT transporters (AZD3965 and Syrosingopine) significantly enhances NAC-induced cytotoxicity...Our data suggests that lactate reprogramming is a targetable susceptibility of NAC treatment. The unique sensitivity of GBM towards NAC and its dependence on lactate as an oncometabolite governing metabolic resistance might open a novel druggable pathway for treating both IDHwt and IDHmut gliomas."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • LDHA

N-acetylcysteine induced lactate reprogramming is a targetable metabolic susceptibility in glioblastoma. (SNO 2025) - "To test the effects of lowering lactate levels on NAC-induced cytotoxicity, we treated glioma cells with the mitochondrial pyruvate dehydrogenase enzyme complex inhibitor dichloroacetate (DCA)...Blocking lactate import/export via inhibition of MCT transporters (AZD3965 and Syrosingopine) significantly enhances NAC-induced cytotoxicity...Our data suggests that lactate reprogramming is a targetable susceptibility of NAC treatment. The unique sensitivity of GBM towards NAC and its dependence on lactate as an oncometabolite governing metabolic resistance might open a novel druggable pathway for treating both IDHwt and IDHmut gliomas."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • LDHA

Synergistic potential of Tucatinib and Dichloroacetate in HER2+ breast cancer: an in vitro analysis (SNO 2025) - "The addition of DCA at 1mM improves the antiproliferative effects of Tucatinib in HER2+ BT474 breast cancer cells. Further studies investigating additional drug combinations and cell lines are ongoing."

Preclinical • Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • HIF1A • PDK1

Safety, pharmacokinetics, and pharmacodynamic effects of dichloroacetate in patients with recurrent glioblastoma (SNO 2025) - "PDK expression and lactate levels are associated with worse cancer outcomes. Combining DCA with standard radiation and chemotherapy could improve outcomes of newly diagnosed GBM patients."

Clinical • PK/PD data • Brain Cancer • Glioblastoma • Metabolic Disorders • Solid Tumor • PCNA • PDHA1 • PDK4 • PGK1

Metabolic regulation of T cell production of IL-10 and IL-22 protects against intestinal inflammation. (PubMed, Precis Clin Med) - "Among tested metabolic inhibitors, dichloroacetate (DCA) significantly enhanced IL-10 and IL-22 production by CD4⁺ T cells...Our findings demonstrate that DCA enhances IL-22 and IL-10 production in Th1 cells through Ahr and Bhlhe40, respectively. These results identify a novel metabolic mechanism by which DCA promotes mucosal immune regulation and highlight its potential as a therapeutic strategy for inflammatory bowel disease."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • CD4 • IL10 • IL22 • PRDM1

Nature-based biological treatment of disinfection byproducts: Transformation pathways from high-molecular-weight aromatics to regulated aliphatics. (PubMed, Bioresour Technol) - "Dichloroacetic acid (DCAA) decayed faster than trichloromethane (TCM)...These findings highlight the need for optimized designs (e.g., SZ saturation ≥ 50 % with controlled multi-day residence) to complete transformation, limit short-term releases, and reduce toxicity. This study advances the mechanistic understanding of DBP dynamics in nature-based solutions, providing actionable strategies for urban runoff management."

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Dichloroacetic Acid Enhances Photodynamic Therapy-Induced Regulated Cell Death in PANC-1 Pancreatic Cancer Cell Line. (PubMed, Int J Mol Sci) - "DCA amplified PDT-induced oxidative stress, overcoming redox defenses and enhancing ferroptotic and immunogenic responses. These findings suggest that combining DCA with PDT enhances multimodal cell death in PDAC, providing a rationale for further in vivo studies to validate this redox-metabolic approach to treating chemoresistant pancreatic tumors."

Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Metabolic immaturity as a hidden driver of FCD (AES 2025) - "Treatment conditions were rapamycin (50 nM, 48 hrs) and dichloroacetate (DCA; 1 mM, 48 hrs), a metabolic modulator that enhances oxidative metabolism by facilitating pyruvate entry into the TCA cycle. We observed that Nprl2 KO N2a cells retain a persistent glycolytic phenotype that is only partially rescued by rapamycin or DCA treatment. These data suggest that neuronal metabolic immaturity is a sustained and targetable feature of mTOR-opathy-associated epilepsy, with implications for future therapeutic strategies aimed at restoring mitochondrial function in FCD. Transcriptomic evidence of persistent metabolic gene dysregulation supports this, and the need for bioenergetic profiling in mTORopathy models and may inform future therapeutic strategies for FCD-associated epilepsy."

CNS Disorders • Epilepsy

Predicting regulated and emerging disinfection byproducts in small drinking water catchments using machine learning. (PubMed, Environ Int) - "Ten DBP parameter concentrations, namely total trihalomethanes, total haloacetic acids, trichloromethane, bromodichloromethane, dibromochloromethane, dichloroacetic acid, trichloroacetic acid, dichloroacetonitrile, trichloronitromethane (chloropicrin) and trichloropropanone could be quantitatively predicted (average R2 = 0.86, root mean squared percent error = 27.9 %) with a further five species classified for binary presence-absence only (95.6 % average accuracy)...Inclusion of hydrochemical parameters (e.g., DOC) only marginally improved model performance. Our findings demonstrate a proof-of-concept for the utility of machine learning models trained on DOM spectroscopic variables using a relatively small sample size (n = 198) with a scalable workflow freely available to further data-driven, risk-based management of DBP formation in drinking water supplies globally."

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