ethacrynic acid / Generic mfg. - LARVOL DELTA

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

Evaluation of the Effectiveness of l-Ergothioneine in Conjunction with Reactive Intermediates Derived from Model Pharmaceuticals. (PubMed, Chem Res Toxicol) - "These drugs included acetaminophen, diclofenac, carbamazepine, clozapine, nefazodone, raloxifene, tamoxifen, ticlopidine, troglitazone, and ethacrynic acid. Notably, our findings suggest that, in addition to scavenging reactive oxygen species, ET can also shield cells from reactive xenobiotic intermediates, similar to GSH. This research presents the first evidence of ET's role as a trapping agent for reactive drug intermediates."

Journal

Diuretic Prescriptions During Postnatal Maturation in Extremely Preterm Infants Admitted to United States Children's Hospitals (ATS 2025) - "We identified all prescriptions of acetazolamide, bumetanide, chlorothiazide, diuretic combinations, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone and spironolactone between NICU admission and hospital discharge. Both furosemide and chlorothiazide are highly prescribed during postnatal age ranges that may span periods of dynamically changing diuretic clearance. High prescription periods occurred earliest for furosemide, whereas chlorothiazide was prescribed most often at discharge. Furosemide and chlorothiazide should be prioritized in developmental pharmacology research to ensure appropriate clinical dosage adjustments throughout infant maturation and appropriate dosage selection in clinical trials evaluating their safety and effectiveness in preterm populations."

Clinical • Prematurity • Pediatrics • Pulmonary Disease • Respiratory Diseases

Design and Synthesis of (2,3-dichloro-4-(3-(substituted Phenyl)acryloyl) phenoxy) Substituted Carboxylic Acid as Potent Glutathione-s-transferase Inhibitors, Anti-breast-cancer Agents and Enhancing Therapeutic Efficacy of Anticancer Agents. (PubMed, Med Chem) - "We have effectively developed novel compounds possessing structural resemblance with ethacrynic acid Compounds of the series has shown moderate to higher inhibitory effect on GSTs and anti-proliferative activity in breast cancer. The compound A3 was found to be promising agent with high level of potency in each biological response. The research studies presented here may be an enlightening path in development of novel therapeutic agents with high level of inhibition in the activity of GSTs and anti-breast cancer effect."

Journal • Breast Cancer • Infectious Disease • Oncology • Solid Tumor • GSTP1

Correlation between PRDX6 levels and freezability properties of sheep semen. (PubMed, Theriogenology) - "Finally, adding a PRDX6 peroxidase activity inhibitor (Ethacrynic acid) or a calcium - independent phospholipase A2 (iPLA2) activity inhibitor (MJ33) to the diluent significantly reduced the freezability parameters of sperm...It suggests that increasing the levels of PRDX6 in sperm may be an effective strategy to improve the quality of cryopreserved semen. Future research can further explore the molecular mechanisms regulating the levels of PRDX6, providing a scientific basis for the optimization of sheep semen cryopreservation techniques."

Journal • PRDX6

Ethacrynic acid mitigates skin fibrosis through downregulation of S100 family damage-associated molecular pattern expression in the epidermis. (PubMed, J Invest Dermatol) - No abstract available

Journal • Fibrosis • Immunology

Inhibition of PINK1 senses ROS signaling to facilitate neuroblastoma cell pyroptosis. (PubMed, Autophagy) - "Specifically, inhibition of PINK1 by AC220 or knockout of PINK1 impairs mitophagy and enhances ROS production, leading to oxidation and oligomerization of TOMM20, followed by mitochondrial recruitment and activation of BAX. Furthermore, inhibition or deficiency of PINK1 potentiates the anti-tumor effects of the clinical ROS-inducing drug ethacrynic acid (EA) to inhibit neuroblastoma progression in vivo. Therefore, our study provides a promising intervention strategy for neuroblastoma through the induction of pyroptosis."

Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • CASP3 • GSDME

Ethacrynic acid inhibits the growth and proliferation of prostate cancer cells by targeting GSTP1 and regulating the PI3K-AKT signaling pathway. (PubMed, Int J Biochem Cell Biol) - "EA inhibits PC progression by binding to GSTP1 to downregulate the activity of PI3K/AKT pathway, and this result suggests the potential of EA to be an anticancer agent for PC therapy."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • GSTP1

Exploring the GSTP1 inhibition potential of photosensitizer compounds for enhanced cancer treatment in photodynamic therapy. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Among the tested photosensitizers, zinc phthalocyanine, hypericin, and temoporfin emerged as the top candidates, exhibiting binding energies of - 10.8, - 10.2, and - 9.8 kcal/mol, along with Ki values of 0.012, 0.033, and 0.064 µM, respectively. These compounds outperformed the reference inhibitor ethacrynic acid, which had a binding energy of - 6.6 kcal/mol and a Ki of 14.35 µM. These findings suggest that the dual action of these photosensitizers provides a promising strategy for combating cancer and overcoming treatment resistance."

Journal • Oncology • GSTP1

Improved intracochlear biopolymeric drug delivery system: an in vivo study. (PubMed, Acta Otolaryngol) - "Twenty-four male Norway Brown rats were randomized into four groups, three of which groups received an intratympanic injection of ethacrynic acid and kanamycin. Two of these groups underwent the placement of an intracochlear microneedle blended or not with dexamethasone, and two groups underwent implantation of a plain microneedle, one of without prior exposure to the ototoxic agent to confirm in vivo biocompatibility...Our intracochlear device demonstrated biocompatibility and produced no hearing changes after its implantation in the control group. Inserted DXM-blended microneedles prevented hearing deterioration in those animals exposed to an ototoxic environment."

Journal • Preclinical • Otorhinolaryngology

Positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes functionalized with ethacrynic acid: Synthesis, characterizaion, and antitumor effect. (PubMed, J Inorg Biochem) - "A new family of ethacrynic acid-functionalized, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes (4a-4e) have been designed, synthesis and fully characterized by 1H and 13C NMR, ESI-MS, elemental analysis, and melting point tests. In addition, the in vivo antitumor effect study on the xenograft mouse models of MCF-7 cells reveal that complex 4e significantly inhibited tumor growth with a higher inhibition efficiency of 68.80 %, in comparison with the groups treated with cisplatin (59.25 %). These results highlight the strong possibility to develop positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes funcionalized with GST inhibitor as promising anticancer agents."

Journal • Oncology

Characterization of Intravenous Ethacrynic Acid within an Academic HealthSystem A Costly Delay in Challenging Sulfa Allergies (ASHP 2024) - No abstract available

Allergy • Immunology

Identification of Boc2Lys-Linked Ethacrynic Acid and Its Analogues As Efficient Glutathione S-Transferase Degraders. (PubMed, ACS Med Chem Lett) - "Based on the similarity of Boc2Lys and Boc3Arg, we identified that Boc2Lys also efficiently induced targeted protein degradation, taking glutathione S-transferase as an example. We found that Boc2Lys-linked ethacrynic acid was able to dose-dependently downregulate the target protein in a mechanism distinct to Boc3Arg."

Journal • Targeted Protein Degradation

Preparation of Glutathione-Regulated Sorafenib Targeted Nanodrug Delivery System and Its Antihepatocellular Carcinoma Activity. (PubMed, ACS Appl Mater Interfaces) - "The preparation process comprises the synthesis of amino-functionalized mesoporous silica nanoparticles (MSN-NH2), surface modification with ethacrynic acid (EA), loading of SOR into the pores, and final surface coating with hyaluronic acid (HA) to obtain SOR@MSN-EA@HA (SMEH) nanoparticles. This results in sustained oxidative stress in the cells, thus enhancing the antitumor efficacy. Both in vitro and in vivo antitumor experiments as well as hemolysis tests have demonstrated that SMEH nanoparticles can accurately target liver cancer cells, effectively downregulate GSH concentration, exhibit good antitumor effects, and possess excellent safety, showing great potential in tumor treatment."

Journal • Hematological Disorders • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Differential interactions of ethacrynic acid and diethyl maleate with glutathione S-transferases and their glutathione co-factor in the house fly. (PubMed, Pestic Biochem Physiol) - "These findings establish in insects that the insecticide synergists EA and DEM function mainly by scavenging the GST co-factor GSH, with some inhibition due to interactions with GSTs and the inhibitor-GSH conjugates, rather than through interaction between the inhibitors and the GST protein itself. These resulting impacts are two-fold, whereby (i) GSH bioavailability is limited and (ii) the GSH-inhibitor complex attenuates GST-based xenobiotic metabolism."

Journal

Lymphatic Endothelial Cell Permeability Is Regulated by Sodium and Nkcc1 (KIDNEY WEEK 2024) - "In addition, furosemide, a Nkcc1 inhibitor, blunted lymphatic vessel pumping dynamics. These results demonstrate that Na+ avid states promote LEC permeability and that bumetanide-induced inhibition of Nkcc1 can further augment this effect. While increasing permeability in lymphatic capillary LECs may be conducive for draining excess interstitial fluid, altering the permeability of LECs in collecting vessels may cause leakage and be detrimental to fluid clearance. In addition, ethacrynic acid may be superior to other loop diuretics due to the lack of off target effects on lymphatic vessel contractility and permeability."

Nephrology • Renal Disease