ethacrynic acid / Generic mfg. - LARVOL DELTA

Crystal structure, intermolecular interactions, Hirshfeld surface analysis, theoretical studies and biological evaluation of (E)-5-(benzyloxy)-2-{[(2,5-dimethoxyphenyl)imino]methyl}phenol, a new Schiff base. (PubMed, Acta Crystallogr C Struct Chem) - "Compared with the corresponding reference inhibitors, BDIMPh showed a slightly higher IC50 value than donepezil for AChE, a slightly lower IC50 value than ethacrynic acid for GST and a higher IC50 value than acarbose for α-glucosidase. These results indicate an enzyme-dependent inhibitory profile rather than uniformly superior activity relative to the reference inhibitors."

Journal • Pain • Tyrosinase

Chloride-dependent mechanisms contribute to urinary bladder smooth muscle contractility: Pharmacological and molecular evidence from rat bladder tissue. (PubMed, Tzu Chi Med J) - "Norepinephrine (NE)-induced contractions were evaluated with pretreatment of chloride transport inhibitors (bumetanide, HEPES without bicarbonate, and ethacrynic acid) and chloride channel blockers (4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid, anthracene-9-carboxylic acid, and niflumic acid) at different concentrations. Expression of ClC-3 and CLCA4 in urothelial and SM layers further suggests that chloride-dependent regulation may involve multiple bladder compartments. Although the precise molecular mechanisms remain incompletely defined, these findings support further investigation into chloride-dependent signaling pathways in bladder physiology and dysfunction."

Journal • Preclinical

Flavonoid-mediated inhibition of ovarian glutathione S-transferase in Schistocerca gregaria: Biochemical characterization and in vitro evaluation. (PubMed, Pestic Biochem Physiol) - "The purified enzyme exhibited maximum activity at pH 8.5 and showed the highest catalytic activity toward 1-chloro-2,4-dinitrobenzene (CDNB), followed by 1,2-dichloro-4-nitrobenzene (DCNB) and ethacrynic acid...Although these findings are based on in vitro biochemical analyses, they suggest that inhibition of ovarian GST may reduce the detoxification capacity of S. gregaria and provide a biochemical basis for future in vivo investigations. Collectively, this study identifies ovarian GST as a potential biochemical target and highlights the potential of flavonoid-based GST inhibitors for further evaluation as synergists in integrated desert locust management."

Journal • Preclinical

Losing More Than Fluid: Diuretic-Associated Agranulocytosis (ACG 2026) - "Introduction: Management of ascites in decompensated cirrhosis includes routine diuretic therapy such as furosemide and spironolactone...The patient was maintained on an increased dose of filgrastim and diuresed with ethacrynic acid instead, with noted improvement in ANC (Table 1)...Figure: Figure 1: Bone marrow core biopsy (H&E, Ã400) showing hypercellular marrow with selective granulocytic aplasia and compensatory erythroid and megakaryocytic hyperplasia. Figure: Table 1: Time course of diuretic administration and filgrastim treatment, white blood cell count, and absolute neutrophil count, demonstrating recovery of agranulocytosis following diuretic discontinuation."

Agranulocytosis • Fibrosis • Granulocytopenia • Hepatology • Immunology • Infectious Disease • Neutropenia

Ethacrynic Oxadiazole 6u Induces Apoptosis by Targeting mTOR/c-Flip Axis and Noxa in Lymphoma Cells. (PubMed, Biol Proced Online) - "6u functions as an apoptosis inducer through the α, β-saturated carbonyl group to decrease c-Flip and to induce Noxa. 6u represents a new type of covalent agent for targeting lymphoma by inducing apoptosis."

Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CFLAR • MCL1

Tau Tubulin Kinase 1 Inhibition Does Not Affect Ciliogenesis And Restores TDP-43 Homeostasis In ALS And FTD-TDP Models (ENCALS 2026) - "Neuroprotective efficacy was evaluated in SH-SY5Y using ethacrynic acid (EA) to induce TDP-43 pathology via glutathione depletion...Furthermore, VNG3.67 restored TDP-43 homeostasis promoting its nuclear localization in the human patient-derived lymphoblast platform.Conclusion We describe VNG3.67 as a selective TTBK1 inhibitor that demonstrates a ciliogenesis-sparing safety profile while showing robust in vitro and in vivo efficacy restoring TDP-43 homeostasis. These findings position VNG3.67 as a promising therapeutic candidate for the treatment of TDP-43 proteinopathies, including ALS and FTD-TDP"

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Proteinopathy • TARDBP

Diuretic Therapy in the Neonatal Intensive Care Unit: A Single-Centre Retrospective Study from the University of Szeged, Hungary (PAS 2026) - "Between 2018 and 2022, 1,331 patients were admitted to the NICU; 246 (18.5%) received diuretic treatment. 68% of patients with gestational age ≤28 weeks, 16% with 29-32 weeks, 8.5% with 33-36 weeks, and 15% with ≥37 weeks received diuretics. Among treated patients, furosemide was the most frequently prescribed (88%), followed by spironolactone (35%), hydrochlorothiazide (30%), and ethacrynic acid (23%)."

Retrospective data • Acute Kidney Injury • Bronchopulmonary Dysplasia • Cardiovascular • Critical care • Heart Failure • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases

Synthesis of Piperazine-Linked Sulfonamide Derivatives and Their Inhibitory Effects on Glutathione S-Transferase: In Vitro and In Silico Approach. (PubMed, Biotechnol Appl Biochem) - "The inhibitory effects of these sulfonamide derivatives on the glutathione S-transferase pi 1 (GSTP1-1) enzyme were evaluated, with ethacrynic acid (INN) serving as a standard inhibitor for comparison...In silico drug-likeness analysis and ADMET predictions of the PLSDs demonstrated that PLSDs showed drug-likeness and had a satisfactory ADMET profile. The structural insights gained from this study offer valuable guidance for the rational design of more potent GSTP1-1 inhibitors, emphasizing the relevance of these scaffolds for future therapeutic developments aimed at targeting GSTP1-1 enzymes."

Journal • Preclinical • GSTP1

A RARE PRESENTATION OF BUMETANIDE INDUCED DRESS SYNDROME (ACC 2026) - "Common triggers include anticonvulsants, allopurinol, and antibiotics, while loop diuretic-associated cases are exceedingly rare...Bumetanide was started 2 weeks before admission, briefly replaced with furosemide; symptoms recurred upon re-initiation... DRESS is challenging to recognize in patients on multiple medications, making careful review of new drugs and dose changes essential. Diagnosis may be supported by drug cessation and re-challenge. This patient had started bumetanide 2 weeks prior to admission; although DRESS typically occurs 2-6 weeks after exposure, delayed onset is possible."

Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Eosinophilia • Heart Failure • Hepatology • Hypertension • Immunology • Inflammation • Nephrology • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

LOOP DIURETIC–ASSOCIATED BULLOUS PEMPHIGOID (WRMC 2026) - "Prior topical corticosteroids provided no relief, and a short prednisone course improved symptoms but was discontinued due to gastrointestinal and behavioral side effects...Despite high-potency topical steroids, doxycycline, and nicotinamide, his symptoms persisted but improved with continued therapy and later dupilumab...Loop and thiazide diuretics share sulfonamide structures and have been linked to allergic skin reactions, whereas ethacrynic acid and spironolactone do not...This case highlights the diagnostic and therapeutic challenges of BP in an elderly patient with complex comorbidities. Awareness of furosemide as a potential trigger is essential, and careful diuretic selection may mitigate risk. We propose the incorporation of electronic medical record alerts to flag high-risk medications and improve recognition of drug-induced BP."

Alzheimer's Disease • Bullous Pemphigoid • Cardiovascular • CNS Disorders • Congestive Heart Failure • Dementia • Dermatology • Dermatopathology • Diabetes • Eosinophilia • Glaucoma • Heart Failure • Hypertension • Immunology • Metabolic Disorders • Ophthalmology • Type 2 Diabetes Mellitus

Glutathione S-Transferases protect against heat-inhibited pollen germination and pollen tube growth in the pistil by regulating proanthocyanidins and fructose to maintain reactive oxygen species homeostasis. (PubMed, J Exp Bot) - "Conversely, application of the GSTs inhibitor ethacrynic acid reversed these beneficial effects. Importantly, exogenous application of FA, PAs, or Fru-either individually or in combination-significantly enhanced spikelet fertility under heat stress. This indicates that GSTs, mediating GSH, play a crucial role in preventing heat-induced pistil dysfunction through the PAs and Fru pathways."

Journal

Dose-Dependent Ototoxicity Effects of Gentamicin and Ethacrynic Acid in a Chinchilla Model of Snhl (ARO 2026) - "In chinchillas, carboplatin exposure selectively targets inner hair cells. These preliminary findings underscore the importance of carefully optimizing gentamicin–ethacrynic acid dosing strategies to selectively damage OHCs without affecting IHCs. Establishing such a protocol will provide a consistent and efficient experimental model of OHC-specific SNHL. Beyond its research value, this model will contribute to the development of more precise diagnostic approaches that can eventually be translated to clinical practice, improving the identification of cochlear pathologies, and guiding more effective therapeutic interventions."

Otorhinolaryngology

Molecular dynamics investigation of single nucleotide polymorphism-driven variations in GSTP1 phosphorylation and substrate interaction. (PubMed, J Biomol Struct Dyn) - "This study evaluated the impact of the rs1695 (Ile105Val) substitution on GSTP1 structural stability, phosphorylation accessibility, and interaction with ethacrynic acid (EA), as a substrate...Overall, the Ile105Val substitution in GSTP1 induces subtle conformational rearrangements that decrease flexibility and modestly reduce EA binding affinity while maintaining overall structural integrity. These findings provide a mechanistic basis for reduced detoxification efficiency and altered phosphorylation regulation, potentially contributing to disease susceptibility."

Journal • GSTP1

Pyrimidine Based Inhibitors Targeting Glutathione S-Transferase in Phase II Detoxification: Antioxidant, ADMET, Docking, and Molecular Dynamics Evaluation. (PubMed, J Biochem Mol Toxicol) - "The data are compared with that of ethacrynic acid (EA), a well-documented GST inhibitor...Other than this, biological activities of GST enzyme complexes were further validated using molecular docking, molecular dynamics, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses. These complementary studies gave further insight into binding affinities, dynamic stability, and pharmacokinetic properties, reinforcing the impact of p1 and p2 complexation on GST structural and functional characteristics."

Journal • P2 data • Brain Cancer • CNS Disorders • Oncology

Deciphering Glutathione S-Transferase P1 Inhibition Mechanisms for Overcoming Cancer Chemoresistance: Insights From Computational Analysis. (PubMed, Proteins) - "Ethacrynic acid (EA) is a known GSTP1 inhibitor; however, the specific molecular mechanisms behind its inhibitory action remain unclear...These findings highlight the need to optimize the lipophilic/hydrophilic balance of future GSTP1 inhibitors to match the physicochemical properties of the binding pocket. Overall, this study offers a deeper understanding of the molecular mechanisms behind GSTP1 inhibition and provides a structural basis for designing targeted therapies to overcome cancer chemoresistance."

Journal • Oncology • GSTP1

Dentin bonding agents and camphorquinone-induced cytotoxicity, 8-isoprostane and prostaglandin production is associated with CYP450, NQO1, NQO2, GST, and GSH peroxidase in human dental pulp cells. (PubMed, Dent Mater) - "DBAs and CQ may affect the inflammatory responses and tissue viability of dental pulp during clinical dental practice. Expression of CYPs, NQO1/NQO2, GST-P and GPx in HDPCs affects the metabolism of CQ, cell viability, 8-isoprostane and PGE2 of HDPCs. Results are important for the clinical success of operative restoration to decrease pulp inflammation and necrosis by modulation of these metabolic enzymes."

Journal • Dental Disorders • Inflammation • CYP1A1 • CYP1A2 • GPX1 • GPX4 • NQO1

Dual Inhibition of AChE and GST by 1,2,4-Triazine-3-Amine: Integrated Biochemical, Computational, and Hepatotoxicity Insights. (PubMed, Biotechnol Appl Biochem) - "Tacrin (Tac) and ethacrynic acid (INN) were used as standard drugs...As a result, it was shown that TzA was a better inhibitor for the AChE enzyme. Furthermore, the binding energies, amino acid residues, and bond lengths of the complexes were determined by molecular docking of the TzA molecule with selected proteins."

Journal • Hepatocellular Cancer • Oncology • Pain • Solid Tumor

Discovery of repurposed ethacrynic acid and its derivatives as novel TEAD inhibitors. (PubMed, Eur J Med Chem) - "Representative compound EA-C15 covalently binds to the TEAD palmitoylation site, blocks palmitoylation and transcriptional activity, and inhibits NCI-H226 cell proliferation and YAP-TEAD target gene transcription at sub-micromolar concentrations. Collectively, these results establish EA and its derivatives as promising TEAD inhibitors that will provide molecular tools and insights for developing YAP-TEAD-targeted anti-tumor therapies."

IO biomarker • Journal • Oncology • CCN1 • CTGF

Preliminary assessment of drug repurposing against virus-associated primary effusion lymphoma. (PubMed, J Microbiol Biol Educ) - "We demonstrate proper quantitative interpretation of the data by using ethacrynic acid, quizartinib, and darapladib as examples. We hope that this practical experimental pipeline will spread awareness of the potential of drug repurposing, especially for diseases like PEL that have unmet clinical needs."

Journal • Epstein-Barr Virus Infections • Hematological Malignancies • Kaposi Sarcoma • Lymphoma • Oncology • Sarcoma • Solid Tumor

Deciphering the quantitative relationship between NRF2 and SRXN1 through semi-mechanistic computational modeling. (PubMed, Toxicology) - "We developed a semi-mechanistic mathematical model based on time course experimental data of NRF2 and SRXN1 protein expression in HepG2 cells following single or repeated exposure to NRF2 activating soft electrophiles (sulforaphane, andrographolide, ethacrynic acid or CDDO-me) at a wide concentration range. Moreover, this modulation of the transcription factor activity of NRF2 is time-, compound- and exposure scenario specific. We conclude that a complete understanding of NRF2-mediated ARE genes activation requires detailed dynamic information on NRF2 binding partners and cofactors."

Journal

Calcium Channel Blockers and Irreversible EGFR TKIS. Opportunities Missed? (IASLC-WCLC 2025) - "Study in cell lines concluded that β-Catenin could become a novel therapeutic target in combination with irreversible EGFR-TKIs, such as Afatinib, but not with reversible EGFR TKIs such as Erlotinib...An ongoing (2024) study of Osimertinib and Tegavivint, a novel ß-catenin / Wnt inhibitor indicate that β-catenin could be a relevant target with Osimertinib, an irreversible EGFR TKI. Another study showed that irreversible EGFR TKI Afatinib and Ethacrynic Acid, a diuretic agent, have strong antitumor effects in vitro and in mice models of EGFR/T790M NSCLC by inhibiting WNT/ß-catenin pathway...Amlodepine or Verapamil are candidates for clinical trials with Afatinib or Osimertinib...Repurposing of existing medications can save patients' time and provide safe, affordable and effective treatments that improve SOC. Industry sponsorship of repurposed drugs and clinical trials are not readily achievable and other mechanisms for financial incentives and sponsorship..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer • ABCB1

Ethacrynic acid regulates gentamicin ototoxicity via the blood-labyrinth barrier. (PubMed, Hear Res) - "This study systematically investigated the ototoxic mechanisms of GM combined with ethacrynic acid (EA) and the protective effects of N-acetylcysteine (NAC) using C57BL/6 J mice. The time-dependent nature of NAC intervention offers a strategy to prevent drug-induced hearing loss. These findings provide critical insights for optimizing clinical regimens involving aminoglycosides and loop diuretics."

Journal • Otorhinolaryngology

Identification of glutathione transferase (GST P1) inhibitors via a high-throughput screening assay and implications as alternative treatment options for breast cancers. (PubMed, PLoS One) - "Ethacrynic acid (a known GST P1-1 inhibitor), ZM 39923, PRT 4165, 10058-F4, and cryptotanshinone were shown to be the most active...Western blot analysis was used to identify the presence of GST P1-1 in the breast cancer cell lines tested. The implications of these results concerning alternative treatment options for breast cancers are discussed."

Journal • Breast Cancer • Oncology • Solid Tumor

The Cytotoxic Effect on HepG2 Cell Line and In Vitro, In Silico Evaluation of 1,2,4-Triazine Compounds as Inhibitors of Acetylcholinesterase and Glutathione S-Transferase. (PubMed, J Biochem Mol Toxicol) - "The results indicated that the inhibitory activity of Tr-1, Tr-2, and Tr-3 was comparable to the standard inhibitor Tacrine (Tac) and Ethacrynic acid (INN), respectively. These findings formed the foundation for biologic activity these compounds with optimized binding properties and anticipated inhibitory activities. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of the Tr-1, Tr-2, Tr-3 molecules were conducted to obtain deeper insights into ADMET properties in AChE and GST candidate inhibitors."

Journal • Preclinical • Liver Cancer • Oncology • Pain • Solid Tumor

Characterization and Immunogenicity Analysis of Glutathi- one S-transferase from Otodectes cynotis. (PubMed, Mol Biochem Parasitol) - "Molecular docking with ethacrynic acid indicated stable binding, suggesting GST as a potential drug target. This study presents the first functional and immunogenic characterization of O. cynotis GST, suggesting its critical role in oxidative stress mitigation and drug detoxification, and supporting its potential as an anti-mite vaccine candidate."

Journal • Otorhinolaryngology