amiloride hydrochloride / Generic mfg. - LARVOL DELTA

ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Laura Huppert, MD, BA | Trial completion date: Mar 2029 ➔ Jun 2029 | Trial primary completion date: Mar 2029 ➔ Jun 2029

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Kidney kallikrein-1 contributes to cleavage of gamma-ENaC in vivo. (PubMed, Am J Physiol Renal Physiol) - "Despite impaired ENaC proteolysis, amiloride-sensitive sodium excretion was preserved, indicating intact ENaC function...However, the absence of overt sodium or potassium handling defects in CNT-Klk1-/- mice suggests that kallikrein-1 deficiency is not sufficient to disrupt overall ENaC function, likely due to compensatory mechanisms from redundant proteolytic or non-proteolytic pathways. Together, our results refine the role of kallikrein-1 as a modulator, rather than a sole determinant, of ENaC activation and highlight the complexity of aldosterone-dependent sodium transport in the distal nephron."

Journal • Preclinical • Targeted Protein Degradation • CALB1

Differential Assembly of Native ENaC Complexes Across Mouse Epithelial Tissues. (PubMed, bioRxiv) - "The tag preserves physiological ENaC function, as ENaCγ-VF mice display normal electrolyte handling, benzamil affinity, and amiloride-sensitive Na⁺:K⁺ responses indistinguishable from wild-type animals...In combination, the ENaCγ-VF line provides a biochemical anchor for identifying regulatory and trafficking proteins that co-purify with native ENaC complexes. These data show that ENaC architecture in vivo is heterogeneous, and establish ENaCγ-VF mice as a platform for dissecting how epithelial environments shape ENaC assembly, composition, and regulation."

Journal • Preclinical

Physiologic profiling using plasma renin activity and aldosterone on blood pressure control among Ghanaian stroke survivors: A pilot trial. (PubMed, Equity Neurosci) - "Participants randomized to the physiologic profiling arm had plasma renin activity and aldosterone levels measured and eplerenone, a mineralocorticoid receptor antagonist, or amiloride was added to their existing BP medications depending on renin-aldosterone profile. Among Ghanaian stroke survivors with RH, the addition of eplerenone to background antihypertensive medications based on plasma renin-aldosterone profile demonstrated a signal of efficacy compared with usual care. A larger study with longer follow-up powered to assess hard cardiovascular outcomes among stroke survivors with uncontrolled resistant hypertension is warranted."

Clinical • Journal • Cardiovascular • Hypertension

Novel frameshift variant in the β subunit of epithelial sodium channels uncovers Liddle syndrome in a young patient with metabolic syndrome: a case report with review of literature. (PubMed, Endocr J) - "The patient was initiated on targeted therapy with amiloride, which rapidly normalized his blood pressure and hypokalemia, thereby confirming the diagnosis...Key steps include obtaining a family history, screening for hypokalemia, evaluating renin and aldosterone levels, and assessing the response to standard therapy. Identifying a rare disorder like Liddle syndrome allows for a paradigm shift in management from empiric to targeted treatment, which is essential for preventing the debilitating long-term sequelae of chronic hypertension."

Journal • Cardiovascular • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Nephrology • Obesity • Rare Diseases

ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Laura Huppert, MD, BA | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

First European case of Geller syndrome complicated with hypokalemic nephropathy: A case report and literature review. (PubMed, Metabol Open) - "Geller syndrome is caused by a gain-of-function mutation in the mineralocorticoid receptor (MR), rendering it prone to activation by elevated progesterone levels during pregnancy...Initial potassium replacement, eplerenone administration and desmopressin were insufficient, whereas the administration of amiloride, a potassium-sparing diuretic that inhibits epithelial sodium channels (ENaC) in the distal nephron, led to complete resolution of the clinical syndrome...Genetic testing was performed in only one case, apart from the initially reported ones. Urgent delivery was required in four cases, while amiloride, the treatment of choice, was administered in only five, highlighting the importance of early recognition of the syndrome for effective management and prevention of adverse pregnancy outcomes."

Journal • Review • Cardiovascular • Diabetic Nephropathy • Hypertension • Metabolic Disorders • Renal Disease

Aldolase a coordinates macropinocytic nutrient scavenging and lysosomal degradation in lung cancer by interacting with V-ATPase. (PubMed, Cell Commun Signal) - "Our study identifies a novel, non-enzymatic function of ALDOA as a critical regulator of lysosomal degradation of macropinocytosed proteins via interaction with V-ATPase. This mechanism is essential for metabolic adaptation and growth of KRAS-mutant tumors under stress conditions. Targeting ALDOA offers a promising therapeutic strategy for cancers that rely on extracellular nutrient scavenging."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALDOA • KRAS

ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Laura Huppert, MD, BA | Trial primary completion date: Dec 2028 ➔ Mar 2029 | Trial completion date: Dec 2028 ➔ Mar 2029

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Receptors and signaling for sour and salty: the ionic taste qualities. (PubMed, Chem Senses) - "In a subset of type II cells, low NaCl concentrations, which are appetitive, pass through the apically located, sodium-selective, and amiloride-sensitive epithelial sodium channel...High concentrations of NaCl, KCl, and NH4Cl, which are aversive, are detected by a different subset of type II cells and type III cells. Although the depolarizing mechanism for high concentrations of NaCl and KCl remains unidentified, NH4CL is detected by OTOP1 in type III taste receptor cells, and the chloride channel TMC4 may contribute to repolarization of the receptor cells, to enhance their responsivity to the salt stimulus."

Journal • Review

Mechanistic insights into opioid-induced pulmonary edema: receptor specificity and sodium transport. (PubMed, Ir J Med Sci) - "Opioid-induced AFC impairment involves receptor-specific alterations in alveolar fluid regulation, with the DOR playing a dominant inhibitory role, suggesting its involvement in the development of pulmonary edema."

Journal • Acute Respiratory Distress Syndrome • Addiction (Opioid and Alcohol) • Anesthesia • Cardiovascular • Pain • Respiratory Diseases

PRL-3 enhances multiple myeloma cell survival in acidic microenvironments via metabolic adaptation and pH regulation. (ASH 2025) - "Pharmacologic inhibition of lactate and proton transport was performed using Syrosingopine (dualMCT inhibitor), AZD0095 (MCT4 inhibitor), AZD3965 (MCT1 inhibitor), Bafilomycin A1 (v-ATPase inhibitor),and ethyl isopropyl amiloride (EIPA; NHE1 inhibitor). Thissuggests compensatory roles among transporters and pathways whose importance varies depending onthe pH level. Increased metabolism and proton transport are associated with high PRL-3 expression,supporting PRL-3 as a key protein for cell survival in acidic conditions and a potential therapeutic targetin myeloma treatment."

Hematological Malignancies • Multiple Myeloma • ANXA5 • PTP4A3 • SLC16A1

Severe lithium-induced nephrogenic diabetes insipidus: The diuresis paradox. (PubMed, S Afr Med J) - "Amiloride with hydrochlorothiazide adequately reduced the polyuria. Management of lithium-induced NDI remains complex, and includes diuretics, which paradoxically reduce polyuria in this setting. Failure to follow up critical results led to profound morbidity, and is a crucial learning point in this case."

Journal • Bipolar Disorder • CNS Disorders • Critical care • Metabolic Disorders • Mood Disorders • Psychiatry • Renal Disease

Molecular Dynamics Insights into TAS1R2 Transmembrane Domain Activation. (PubMed, Int J Mol Sci) - "Previous studies demonstrated that the sweetener S819 and the sweet inhibitor amiloride act through the transmembrane domain (TMD) of TAS1R2; however, the molecular mechanisms underlying these ligand-specific effects remain unclear, largely due to the historical lack of experimentally determined full-length STR structures...Additional analyses uncovered ligand-specific rearrangements in hydrogen-bonding and hydrophobic interaction networks. These results provide atomistic insights into how agonists and antagonists differentially modulate TAS1R2 activation and lay a structural foundation for designing novel sweeteners and taste modulators."

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Amiloride: revisiting an old drug for resistant hypertension. (PubMed, Clin Hypertens) - "The findings from the SPARE trial suggest that amiloride may be a viable alternative to spironolactone for RH, particularly in patients who are intolerant to mineralocorticoid receptor antagonists. While spironolactone remains the preferred option due to its established role in blocking systemic aldosterone activation and proven cardiovascular benefits, amiloride can provide a practical and well-tolerated alternative."

Journal • Review • Cardiovascular • Fibrosis • Hypertension • Immunology • Women's Health

Polystyrene nanoplastics promote fish iridovirus replication via inducing inflammatory response, antioxidant damage and enhancing viral entry. (PubMed, Environ Pollut) - "In contrast, methyl-β-cyclodextrin and ethyl-isopropyl amiloride treatment exhibited no regulatory effects, suggesting that PS-NPs internalization and promoted SPIV replication via the clathrin-mediated endocytosis in vitro. Overall, our findings offer new insights into the pro-viral actions of PS-NPs on fish iridovirus infection in vitro, which highlights a potential threat of NPs to aquatic viral diseases."

Journal • Infectious Disease • Inflammation

APAM: Acid-Sensing Ion Channel and Migraine Disease Proof of Concept Study on the Efficacy of Amiloride in the Prophylaxis of Migraine Aura (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Centre Hospitalier Universitaire de Nice | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

Ovarian Hormones Moderate Systolic Hypertension in Female Eln Haploinsufficient Mice. (PubMed, bioRxiv) - "Furthermore, amiloride lowered SBP and increased urinary Na + excretion, suggesting that Eln +/- -induced hypertension may be Na + -dependent. We conclude that increased Na + and water retention by the kidney contribute to hypertension resulting from Eln haploinsufficiency. The underlying mechanism involves the alteration of ovarian hormone effects in the kidney and sustained signaling downstream of the V 2 receptor, leading to increased ENaC activity and water reabsorption."

Journal • Preclinical • Cardiovascular • Developmental Disorders • Genetic Disorders • Hypertension

Copper uptake in blue crabs is independent of sodium transport under hyposaline conditions. (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "Specific inhibitors targeting Na+/H+ exchangers (amiloride, 100 μM) and Na+, K+, 2 Cl- cotransporters (NKCC) (furosemide, 120 μM) were used. The 64Cu accumulated mainly in the carapace (49 %) and posterior gills (22 %), regardless of Na+ availability. The findings clearly demonstrate that Cu uptake, irrespective of the uptake pathway, proceeds independently of Na."

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Na+/H+ Exchanger 1 Inhibition Overcomes Venetoclax Resistance in Acute Myeloid Leukemia. (PubMed, Cells) - "Our results demonstrated that co-treatment with venetoclax and the NHE1 inhibitor 5-(N,N-hexamethylene) amiloride (HMA) synergistically induced apoptosis in both venetoclax-sensitive and -resistant leukemic cell lines. Furthermore, co-treatment downregulated the anti-apoptotic protein MCL-1 and reduced PI3K and Akt phosphorylation, suggesting that inhibition of these survival pathways also contributed to the synergistic effect. Inhibition of NHE1 may substantially enhance venetoclax sensitivity in certain AML models, particularly in venetoclax-resistant THP-1 cells but not in U-937, highlighting biological diversity and the probable involvement of alternative survival pathways."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BAX • CASP3 • CASP9 • MCL1

Piezo1 Mediates Deoxycorticosterone Acetate-Salt Hypertension Through Renal Epithelial Sodium Channel Activation in the Kidneys (KIDNEY WEEK 2025) - "Yoda1 markedly induced increased Na + influx in mpkCCD cells, which was significantly blocked by amiloride. ICG001 significantly attenuated the mechanical force or Yoda1-induced upregulation of β-catenin and ENaC subunits. Conclusion Piezo1 activation induced increased blood pressure likely through upregulating ENaC expression in the kidney of mice with DOCA-salt by activating β-catenin pathway."

Cardiovascular • Hypertension • Nephrology • Renal Disease

Amiloride Is Noninferior to Spironolactone for Resistant Hypertension. (PubMed, Am Fam Physician) - No abstract available

Journal • Cardiovascular • Hypertension

ATP increases murine neuroblastoma cell size through a PANX1- and macropinocytosis-dependent mechanism. (PubMed, Biol Open) - "Amiloride treatment and mutation of an extracellular tryptophan (W74) in PANX1 abolished ATP-evoked cell area enlargement, suggesting that PANX1 may itself regulate this form of macropinocytosis...Several lipid-PANX1 interactions were identified with relevance to macropinocytic mechanisms. The role of PANX1 in ATP-mediated macropinocytosis could be particularly important for disease states implicating PANX1, such as cancer, where ATP can act as a purinergic regulator of cell growth/metastasis and as a supplementary energy source following internalization."

Journal • Preclinical • Neuroblastoma • Oncology • Solid Tumor

Lysosomal Membrane Permeabilization Sensitizes Ctss-Hyperactive Tumors to BCL2-Targeting Therapies (ASH 2023) - "We next employed LMP-inducing tool compounds (LLOMe) and clinically used drugs or analogs (desipramine, hexamethylene amiloride) to release cathepsins into the cytosol...The combination of LLOMe-induced LMP and the BCL2 inhibitor venetoclax (VEN) showed increased cytotoxicity in CTSS-hyperactive Karpas422 cells compared to monotherapy and CSTB k/d enhanced this phenotype (Fig A, bottom)...In summary, we show that CSTB is a functionally relevant inhibitor that determines the net activity of LMP-released cytosolic CTSS. Furthermore, LMP-inducing therapies may be a promising approach to sensitize CTSS-hyperactive tumors towards apoptosis by proteolytic cleavage of BCL2 family members."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BCL2 • BCL2L1 • CTSS • MCL1

Drug-associated hypertensive crisis: a disproportionality analysis of the FAERS database. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Ramipril (282 cases) and valsartan (192 cases) ranked as the second and third medications, respectively. The top 5 drugs associated with the risk of hypertensive crisis under the ROR algorithm were amlodipine perindopril (ROR = 136.64), methyl aminolevulinate (ROR = 122.78), tranylcypromine (ROR = 105.15), rifapentine (ROR = 39.46), and amiloride hydrochlorothiazide (ROR = 39.36)...Our study showed that numerous medications carry potential risks for drug-associated hypertensive crisis. Further investigation is required to establish causality and inform clinical decision-making."

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