zafirlukast / Generic mfg. - LARVOL DELTA

In Silico identification of inhalable small-molecule IL-33/ST2 antagonists for severe type-2-high asthma endotypes. (PubMed, Sci Rep) - "Zafirlukast emerged as the top-ranked scaffold with a docking score of - 7.3 kcal/mol...Collectively, these results prioritize a non-biologic, ST2-directed small-molecule scaffold for further investigation and provide a computational framework to support subsequent experimental validation, including biochemical and cellular studies, in the context of severe type-2-high asthma. As this is a purely in silico study, the findings are hypothesis-generating and do not demonstrate functional inhibition of the IL-33/ST2 interaction; experimental validation is required."

Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL33

Sine oculis homeobox 1 drives endothelial dysfunction in preclinical pulmonary arterial hypertension. (PubMed, Sci Transl Med) - "Endothelial-specific Six1 knockout improved pulmonary hemodynamics, endothelial dysfunction, pulmonary artery remodeling, and right ventricular function in SU5416/hypoxia (SuHx)-induced PH mice...Structure-based virtual screening and surface plasmon resonance analysis demonstrated that zafirlukast was an inhibitor of SIX1 transcriptional activity...Overall, we found that SIX1 was a driver for endothelial dysfunction and PH through regulating MAST4 transcription and subsequently MAPK1/3 activation. Targeting SIX1 may be a promising strategy for PAH treatment and drug development."

Journal • Preclinical • Cardiovascular • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • EDN1 • MAPK1 • MAST4 • SIX1

Isoquercetin and Zafirlukast Cooperatively Suppress Tumor Growth and Thromboinflammatory Signaling in a Xenograft Model of Ovarian Cancer. (PubMed, FASEB J) - "ISOQ also potentiated standard cisplatin/gemcitabine chemotherapy. Notably, the combination of low-dose ISOQ plus ZAF achieved ≥ 80% inhibition of key tumor-associated markers at one-third the monotherapy dose and outperformed either agent alone. These findings support ISOQ and ZAF as promising agents for the treatment of cancer and CAT and establish thiol isomerase inhibition as a strategy to simultaneously target thrombosis, tumor progression, and immune escape."

IO biomarker • Journal • Preclinical • Cardiovascular • Hematological Disorders • Oncology • Ovarian Cancer • Solid Tumor • Venous Thromboembolism • PDIA3 • PD-L1

Early AI-driven repurposing study of existing drugs towards the vasopressin V2 receptor. (PubMed, Comput Biol Med) - "Five drugs were shortlisted as promising candidates for V2R: cabergoline, clopidogrel, cloxacillin, perphenazine, and zafirlukast...Interestingly, zafirlukast, at single-digit nanomolar concentration significantly reduced the DDAVP-dependent cAMP production and water reabsorption, with effects comparable to tolvaptan, a well-known selective V2R antagonist...Induced-fit docking simulations demonstrated that zafirlukast engages V2R by adopting a binding conformation closely resembling that of X-ray solved vasopressin. Taken together, our results support the repurposing of zafirlukast as a promising V2R antagonist candidate."

Journal • Oncology • CD4

Discovery of Essential Genes as Possible Targets for Prostate Cancer Drug Development. (PubMed, Int J Genomics) - "Following that, we considered these possible genes as targets for drugs, performed docking analysis with 255 meta-drug agents, and identified the top 10 candidate drugs (adapalene, ergotamine, imatinib, dutasteride, vistusertib, risperidone, zafirlukast, irinotecan hydrochloride, drospirenone, and telmisartan). This study uniquely combines multidataset transcriptomic integration, HubG prioritization, and MD validation to propose novel biomarker-drug pairings for PCa. The findings offer promising leads for future experimental and clinical validation."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BIRC5 • CDCA5 • NUSAP1

An ELISA for discovering protein-protein interaction inhibitors: blocking lysinoalanine crosslinking between subunits of the spirochete flagellar hook as a test case. (PubMed, SLAS Discov) - "Screening a library of ∼700 compounds with the ELISA confirmed that hexachlorophene, currently the only known inhibitor of Lal crosslinking in FlgE, effectively inhibits the crosslinking reaction. In addition, the assay identified two new potential inhibitors, honokiol and zafirlukast, and several activators which belong to well-known classes of antibiotics."

Journal • Developmental Disorders • Infectious Disease

Cysteinyl leukotriene receptor 1 regulates cellular glucose levels in human retinal cells. (PubMed, Mol Vis) - "Primary human ECs, PCs, and the ARPE-19 cell line were cultured under standard (5.5 mmol/l glucose + 27.5 mmol/l mannitol) and high-glucose (33.0 mmol/l) conditions in the absence and presence of the specific CysLTR1 antagonists montelukast and zafirlukast for 1, 3, and 7 days. Interestingly, the effect of CysLTR1 activity on glucose levels was reversed under acute metabolic stress. Thus, the activity of CysLTR1 appears to be more complex in terms of glucose metabolism and needs to be studied in more detail."

Journal • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Retinal Disorders • Type 2 Diabetes Mellitus

An ELISA for discovering protein-protein interaction inhibitors: blocking lysinoalanine crosslinking between subunits of the spirochete flagellar hook as a test case. (PubMed, bioRxiv) - "Screening a library of ∼700 compounds with the ELISA confirmed that hexachlorophene, currently the only known inhibitor of Lal crosslinking in FlgE, effectively inhibits the crosslinking reaction. In addition, the assay identified two new potential inhibitors, honokiol and zafirlukast, and several activators which belong to well-known classes of antibiotics."

Journal • Infectious Disease

LC-MS-based metabolomics revealed promising role of leukotriene receptor antagonists against colorectal cancer. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "These findings demonstrate the antiproliferative potential of montelukast and zafirlukast in CRC and provide new insights into their distinct molecular mechanisms of action. This supports their potential repurposing as adjunctive therapies in CRC treatment."

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

Structural elucidation of Langat virus helicase unveils dual-target inhibition for broad-spectrum anti-flaviviruses strategy. (PubMed, Front Cell Infect Microbiol) - "Zafirlukast emerges as a promising prototype for dual-target inhibitors, capable of simultaneously obstructing ATP hydrolysis and RNA unwinding. These findings provide a strong foundation for designing novel broad-spectrum therapeutics against neurotropic flaviviruses."

Journal • Dengue Fever • Infectious Disease

Radical-induced Lipid Oxidation Produces a Torrent of Leukotriene-like Agonists in Severe Asthma. (PubMed, J Allergy Clin Immunol) - "Urinary øLTs are new biomarkers that may facilitate non-invasive assessment of asthma severity and the efficacy of therapeutic measures. Presumably øLTs contribute to CysLT receptor-mediated inflammation through CysLT-like inflammatory biological activities previously ascribed uniquely to CysLTs. øLTs provide a mechanistic link between radical-induced biochemistry, activation of the ERK/Akt pathway and asthma. These discoveries require re-examination of long-held disease paradigms for the involvement of CysLTs in asthma pathology and reconsideration of the mechanistic basis for the efficacy of CysLT receptor antagonists for ameliorating chronic asthma. Inhibiting the biosynthesis of øLTs may provide new therapeutic strategies for preventing asthmatic inflammation."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs. (PubMed, Commun Biol) - "We employed a structurally defined homomeric channel chimera (8C-8A(IL125)) and heteromeric LRRC8A/LRRC8C (8A/8C) channels to investigate the mechanism of action of two structurally distinct LRRC8 inhibitors: zafirlukast and pranlukast. The association between voltage-dependent inactivation induced by mutations or low pH and inhibitor sensitivity suggests that drug inhibition involves disruption of protein-lipid interactions and destabilization of the pore. This may represent a common mechanism of LRRC8 channel inhibition by lipophilic drugs."

Journal • LRRC8A

Exploration common biomarkers and pathogenesis of primary Sjögren's syndrome and interstitial lung disease by machine learning and weighted gene co-expression networks. (PubMed, PLoS One) - "This study revealed that CYSLTR1 and SIGLEC10 demonstrate diagnostic potential for pSS-ILD. Their mechanism of action likely involves synergistically upregulating memory B cells to promote disease progression. Furthermore, we identified montelukast as a potential therapeutic agent. This discovery holds promise for improving clinical outcomes for pSS-ILD patients."

Biomarker • Journal • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Sjogren's Syndrome • CD4 • FOXC1 • MIR195 • MIR26A1 • MIR27A • SIGLEC10

Crossover Study of Zafirlukast in Preventing Allergen-induced Signs and Symptoms in Response to Cat Dander Challenge (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Allergy & Asthma Medical Group & Research Center | Trial completion date: Jul 2024 ➔ Jul 2026 | Trial primary completion date: Jun 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • Allergic Rhinitis • Allergy • Immunology • Inflammation

The specialised pro-resolving mediators protectin D1 and maresin 1 dampen IL-13-induced airway hyperreactivity in isolated human airways (ERS 2025) - "Incubation with zafirlukast did not influence PD1 or MaR1. Conclusion PD1 and MaR1 reduced IL-13-induced AHR to LTD4 and histamine. Certain SPMs should be evaluated as potential therapies of AHR."

Asthma • Immunology • Respiratory Diseases • IL13 • PD-1

Repurposing zafirlukast confers renal protection in ischemia-reperfusion injury via suppressing macrophage METosis. (PubMed, Int Immunopharmacol) - "Given its established safety profile, ZFK could bypass Phase I trials, accelerating clinical translation as a safer alternative to calcineurin inhibitors. Our findings also highlight the broader potential of ZFK in METs-related diseases (e.g., sepsis, atherosclerosis) and underscore drug repurposing as a strategic approach for rapid therapeutic development."

Journal • Acute Kidney Injury • Asthma • Atherosclerosis • Cardiovascular • Diabetes • Immunology • Infectious Disease • Inflammation • Nephrology • Pulmonary Disease • Renal Disease • Reperfusion Injury • Respiratory Diseases • Septic Shock • Transplantation

C(sp3)H/N(sp2) Cross-Coupling Reaction for the Synthesis of Tertiary Arylamines via Fluxional SOX·Pd(II) Catalysis. (PubMed, J Am Chem Soc) - "The generality of this reaction enables facile synthesis of six pharmaceuticals and derivatives (e.g., zafirlukast) and five late-stage drug fragment couplings (e.g., flutamide-duloxetine). Phosphoric acids promote the reaction by affording a significant increase in the functionalization rate, rendering a lower energy allylic C-H cleavage as the rate-determining step. We anticipate that this reaction will find broad use in the discovery of complex and medicinally relevant N-alkyl arylamines and that the mechanistic insights will be leveraged to improve efficiencies of other metal-catalyzed aminations."

Journal

Integrative Mendelian randomization and multi-omics analysis identifies anti-allergic drug targets associated with cardiovascular disease risk. (PubMed, Sci Rep) - "Notably, prednisone (targeting ITGB2, TG) and loratadine (targeting TSHR) elevated CVD risk, while zafirlukast (targeting KAT2A, POLB, BAZ2B) reduced it. Pharmacovigilance analysis indicated an increased risk of adverse cardiovascular outcomes with the concurrent use of prednisone and cardiovascular drugs. The comprehensive analyses indicate that certain anti-allergic drugs may heighten the risk of CVDs, suggesting caution with medications like prednisone."

Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Myocardial Infarction • ITGB2 • POLG2

Influence of the Blockage of TNFα and Its Receptors on Bregs-TLR-Induced Allograft Survival (WTC 2025) - "In contrast to the Bregs-TLR and CD120b blockage group, the recipients receiving Bregs-TLR and CD120a blockage (Zafirlukast) prolonged islet graft function (Bregs-TLR with CD120a blockage MST: 21 days vs Bregs-TLR with CD120b blockage MST 13 days, P < 0.01). TNF-α/CD120a/CD120b axis regulates the function of Bregs-TLR and Bregs-TLR-induced allograft survival. Graft rejection after transfer of Bregs-TLR and CD120b bloackge may indicate a TNF-α/CD120b dependent mechanism for the function of Bregs-TLR and Bregs-TLR-induced allograft survival."

Diabetes • Inflammation • Metabolic Disorders • Transplant Rejection • TLR4 • TNFA • TNFRSF1A • TNFRSF1B

Leukotriene Receptor Antagonists for the Prevention and Treatment of Capsular Contracture: A Systematic Review and Meta-analysis. (PubMed, Cureus) - "Leukotriene receptor antagonists (LRAs), such as montelukast and zafirlukast, have been investigated for their anti-inflammatory and anti-fibrotic properties as potential preventive and therapeutic agents for CC. This systematic review and meta-analysis indicate that LRAs, particularly zafirlukast, are effective in reducing the severity and recurrence of CC, especially in its early stages. Further high-quality clinical trials are warranted to establish standardized guidelines for the use of LRAs in the management of CC."

Journal • Retrospective data • Review • Fibrosis

Blocking leukotriene receptors improve experimentally induced gastric ulcers in rats by inhibiting inflammation and apoptosis. (PubMed, Int J Immunopathol Pharmacol) - "Rats were orally administered a single oral dose of 80 mg/kg of indomethacin to induce GU. This is demonstrated by a decrease in the levels of NFκB, TNF-α, and IL-1β, along with an increase in the levels of IL-4 and IL-10. Additionally, Zafirlukast exerted anti-apoptotic effects by downregulating the expression of JNK, PKB, and caspase-3."

Journal • Preclinical • Gastrointestinal Disorder • Inflammation • Oncology • Peptic Ulcer • CASP3 • IL10 • IL1B • IL4

Targeting inflammation-driven tumor progression with Zafirlukast via modulation of Jagged-1/Notch-1/Hes-1, Wnt-4/β-catenin, and VEGF signaling pathways in mice. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Zafirlukast exhibits potent anti-tumor activity by targeting multiple oncogenic pathways, highlighting its potential as a therapeutic option for solid tumors and warranting further clinical investigation."

Journal • Preclinical • Hematological Disorders • Oncology • Solid Tumor • CASP3 • CCND1 • HES1 • IL6 • MMP2 • MMP9 • NOTCH1 • PCNA • TNFA • TP53

Repurposing High-Throughput Screening Reveals Unconventional Drugs with Antimicrobial and Antibiofilm Potential Against Methicillin-Resistant Staphylococcus aureus from a Cystic Fibrosis Patient. (PubMed, Antibiotics (Basel)) - "After performing a literature review to identify other, already published biological properties that could be relevant to the CF lung environment (i.e., activity against other CF pathogens, and anti-inflammatory and anti-virulence potential), the most interesting hits were the following: 5-(N,N-Hexamethylene)-amiloride (diuretic), Toremifene (anticancer), Zafirlukast (antiasthmatic), Fenretide (anticancer), and Montelukast (antiasthmatic) against planktonic S. aureus cells; Hemin against biofilm formation; and Heparin, Clemastine (antihistaminic), and Bromfenac (nonsteroidal anti-inflammatory) against established biofilms. These findings warrant further in vitro and in vivo studies to confirm the potential of repurposing these compounds for managing lung infections caused by S. aureus in CF patients."

Journal • Asthma • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases

Non-surgical Treatment and Prophylaxis of Capsular Contracture in Mammary Implants: A Systematic Review of Literature. (PubMed, Aesthetic Plast Surg) - "Capsular contracture in initial stages (I-II) may have a clinical treatment and prophylaxis. Some medications studied to prophylaxis and treatment of capsular contracture are leukotriene inhibitors, tamoxifen, angiotensin-converting enzyme inhibitors, beta-blockers, pirfenidone and botulinum toxin."

Journal • Review • Fibrosis • Immunology

Efficacy and safety of maintenance regimens for adolescent and adult asthmatics with exercise-induced bronchospasm: Systematic review and network meta-analysis. (PubMed, J Allergy Clin Immunol Pract) - "Low-dose ICS and as-needed ICS-formoterol were equally effective in managing asthmatics with EIB. Adding anti-leukotrienes or LABA to ICS should be considered for more severe cases, with close monitoring to assess treatment response and detect potential tachyphylaxis or AEs."

Journal • Retrospective data • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases