Onon dry syrup (pranlukast) / Ono Pharma - LARVOL DELTA

G Protein: β-Arrestin Bias Confers Differential Regulation of Gαq Signaling by GPR17 Antagonists. (PubMed, ACS Chem Neurosci) - "These findings highlight an unappreciated potential for biased signaling in the pharmacology of GPR17 ligands. We anticipate that these insights will help to inform the translation of GPR17-targeted therapies and improve our understanding of GPR17-mediated signaling pathways in governing myelination."

Journal • CNS Disorders • Solid Tumor • ARRB1

A FRET-Based High-Throughput Screening Assay for the Discovery of Mycobacterium tuberculosis DNA ADP-Ribosylglycohydrolase DarG Inhibitors. (PubMed, ACS Infect Dis) - "Notably, pranlukast did not inhibit human macrodomains, indicating strong selectivity for bacterial targets. Since pranlukast has previously been reported to reduce M. tuberculosis burden, further investigation into its action mechanism in this context would be valuable."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

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

Recent advances in mucopolysaccharidosis IVA treatment. (PubMed, Orphanet J Rare Dis) - "Although enzyme replacement therapy (ERT) with elosulfase alfa is currently the only approved treatment, its clinical benefit on bone pathology is limited due to rapid clearance and poor penetration into avascular cartilage. Strategies to enhance enzyme stability and targeting, such as PEGylated hydrogels and extracellular vesicles, have shown promise in enhancing the biodistribution and stability of GALNS, while pharmacological chaperones, including ezetimibe, pranlukast, and bromocriptine, seem to stabilize GALNS in vitro...Importantly, recent evidence revealed that mitochondrial dysfunction in chondrocytes may contribute to the pathology of MPS IVA, uncovering new targets beyond GALNS enzyme activity recovery. This review highlights recent advances in the treatment of MPS IVA and discusses new directions to improve outcomes in MPS IVA treatment."

Journal • Review • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Predicting Food Effect On Oral Drug Absorption For Solubility-Epithelial Membrane Permeation-Limited Cases With Bile Micelle Solubilization. (PubMed, Pharm Res) - "FaRLS appropriately predicted the food effect for the SL-E drugs. The mechanism was experimentally confirmed by μFlux."

Journal

First-time exploitation of Pranlukast's intrinsic fluorescence: a novel cetrimide-enhanced spectrofluorimetric platform for pharmaceutical, plasma, and content uniformity analysis. (PubMed, RSC Adv) - "This work introduces the first spectrofluorimetric approach for PNK, offering advantages of simplicity, low cost, high sensitivity, and environmental sustainability compared to previously reported UV and chromatographic methods. The method's limitation lies in its reliance on a micellar medium, which may require optimization for other surfactants or biological matrices."

Journal

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

Evidence that Mast Cells Regulate the Cough Hypersensitivity Associated with Eosinophilic Bronchitis. (PubMed, Lung) - "These results suggest that mast cells and not eosinophils may be essential to the emergence of cough hypersensitivity in EB. We speculate that therapeutic strategies targeting mast cells, cysLT1 receptors, and TP receptors may represent endotype-specific treatments for chronic cough."

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

Polypharmacology translates between species and phylogenetic distance: A functional, bioinformatic, and structural study on organic anion transporting polypeptides. (PubMed, Biochem Pharmacol) - "The bioactivity of Pranlukast (PRA) on human OATPs could be accurately predicted based on its activity on drOatp1d1. The collection of pan-ABC transporter modulators also showed activity against other zebrafish (i.e., drAbcb4) and non-zebrafish (i.e., mumAbca1) membrane transporters, ultimately rendering it a suitable tool to translate between species to tackle the undruggability of membrane transporters and potentially other proteins by addressing conserved structural motifs."

Journal • ABCA1 • SLCO2B1

Distinct effects of synthetic GPR17 antagonists on cellular signaling in recombinant HEK293 cells and native oligodendroglial cell backgrounds (CINP-AsCNP 2025) - "These findings reveal a hitherto unappreciated potential for biased signalling in the pharmacology of GPR17 ligands with implications for their regulation of downstream cellular signalling relevant to myelination. We anticipate these insights will expedite the translation of GPR17 targeted therapies and improve our understanding of signaling pathways used by this receptor for governing myelination."

CNS Disorders • Psychiatry • Solid Tumor • ARRB1

Therapeutic potential of Pranlukast against cuprizone-induced inflammatory demyelination and sensory impairment in mice: comparison with Fingolimod. (PubMed, Neurotoxicology) - "Cuprizone and Pranlukast groups presented more microglia/macrophages in the CC, but fewer presenting reactive microglia/macrophages and less NOS2 staining in pranlukast-treated when compared to the cuprizone group, while fingolimod treatment prevented the increase in Iba1 in the CC. In summary, this study demonstrated that pranlukast is a good candidate as a novel drug for use in conditions of inflammatory demyelination, such as MS, by restoring function through modulation of the inflammatory environment."

Journal • Preclinical • CNS Disorders • Inflammation • Multiple Sclerosis • MBP • NOS2

Practical Application and Caution for Interaction Between Antiseizure Medications and Popular Pediatric Medications (AES 2024) - "The patients in Group A had combination of some of CBZ, CLB, CZP, perampanel (PER), ZNS, RUF, STP, VPA, LTG and bromide. Five cases took clarithromycin (CAM) (with pranlukast (PK) in one case and with PK and acetaminophen (AA) in one case), four cases had dextromethorphan (DM) (with cyproheptadine (CH), with tipepidine (TP), and with CH and TP in one case each), and two cases had TP (with AA in one case)... As ASM levels are elevated by concomitant CPMs which metabolizing enzymes inhibit or compete with those of ASM, we must be aware of metabolizing enzymes in both medications. It may lead to detect effective ASMs and to avoid adverse effects, particularly for CPMs which inhibit metabolic enzymes of ASMs. Pediatricians are not aware of interaction of ASMs and CPMs, and we should remind this to patients who take corresponding ASMs and PCMs to avoid adverse events."

Clinical • CNS Disorders • Epilepsy • Infectious Disease • Pediatrics • Pneumonia • Respiratory Diseases • CYP3A4

In silico Prediction of Pranlukast as a Stabilizer of PD-L1 Homodimers. (PubMed, Anticancer Agents Med Chem) - "Our results suggest that pranlukast inhibits the PD-1/PD-L1 axis, meriting its repurposing as an antitumor drug."

Journal • Asthma • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • PD-L1

Neuropsychiatric events related to montelukast and pranlukast in adults with asthma and rhinitis: A 10-year nationwide population-based study. (PubMed, J Allergy Clin Immunol Pract) - "Increased neuropsychiatric risk was observed within 6 months after LTRA prescription. LTRA may lower the threshold for NPEs in those at risk for NPEs, irrespective of sex."

Journal • Asthma • CNS Disorders • Immunology • Inflammation • Psychiatry • Pulmonary Disease • Respiratory Diseases • Sleep Disorder

Site-specific immobilization of Cysteinyl leukotriene receptor 1 through enzymatic DNA-protein conjugation strategy for lead screening. (PubMed, J Chromatogr A) - "The binding of pranlukast, zafirlukast, and MK571 to the immobilized CysLTR1 was realized, and the association constants presented good agreement between the two methods. Rosmarinic acid was retained in the immobilized CysLTR1 column, and the in-vitro test revealed that the compound binds to the receptor in one type of binding site mode. Despite these results, we concluded that the DNA-protein conjugate strategy will probably open up the possibilities for capturing other functional proteins in covalent and site-specific modes from the complex matrices and the immobilized receptor preserves the potential in fishing out lead compounds from natural products."

Journal

Antimycobacterial and healing effects of Pranlukast against MTB infection and pathogenesis in a preclinical mouse model of tuberculosis. (PubMed, Front Immunol) - "Interestingly, PRK treatment improved tissue repair and inflammation resolution by increasing the populations of arginase 1 (Arg-1) and Ym1+Ym2 (chitinase 3-like 3) positive macrophages. In summary, our study found that PRK is useful not only for reducing the tubercular burden but also for promoting the healing of the diseased tissue."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition. (PubMed, Eur Heart J) - "ALDH2 deficiency exacerbates myocardial I/RI by promoting NETosis via the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/LTC4/NOX2 pathway. This study hints at the role of NETosis in the pathogenesis of myocardial I/RI, and pranlukast might be a potential therapeutic option for attenuating I/RI, particularly in individuals with the ALDH2 mutation."

Journal • Cardiovascular • Myocardial Infarction • Reperfusion Injury • ALDH2 • MPO

Benzopyrone, a privileged scaffold in drug discovery: An overview of FDA-approved drugs and clinical candidates. (PubMed, Med Res Rev) - "One of the pioneering anticoagulant drugs, warfarin approved in 1954 bears a benzo-α-pyrone (coumarin) nucleus. The widely investigated psoriasis drugs, methoxsalen, and trioxsalen, also contain a benzo-α-pyrone nucleus...The role of the pyrone core in biological activity has also been discussed. The present review unravels the potential of benzopyrone core in medicinal chemistry and drug development."

FDA event • Journal • Review • Asthma • Dermatology • Immunology • Psoriasis • Pulmonary Disease • Respiratory Diseases

Chemoprevention of esophageal adenocarcinoma in a rat surgical model by a cysteinyl leukotriene receptor‑1 antagonist. (PubMed, Oncol Lett) - "Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL-8 and VEGF."

Journal • Preclinical • Barrett Esophagus • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroenterology • Gastroesophageal Cancer • Gastroesophageal Reflux Disease • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CD68 • CXCL8 • LOX

Computational screening of biomarkers and potential drugs for arthrofibrosis based on combination of sequencing and large nature language model. (PubMed, J Orthop Translat) - "Our study demonstrated that GPR17 holds significant promise as a potential biomarker and therapeutic target for arthrofibrosis. Moreover, pranlukast and montelukast targeted to GPR17 that could be instrumental in the treatment of AF."

Biomarker • Journal • Fibrosis • Immunology • Orthopedics • Pain • Rheumatology

The risk of neuropsychiatric adverse events with use of leukotriene receptor antagonists in patients with asthma: analysis of Korea's National Health Insurance Sharing Service database. (PubMed, J Allergy Clin Immunol Pract) - "We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period."

Adverse events • Journal • Reimbursement • US reimbursement • Allergy • Asthma • Immunology • Mood Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases

Development of an assay pipeline for the discovery of novel small molecule inhibitors of human glutathione peroxidases GPX1 and GPX4. (PubMed, Redox Biol) - "Additionally, every GPX1 inhibitor identified (including omapatrilat, tenatoprazole, cefoxitin and ceftibuten) showed similar inhibitory activity against GPX2...Compounds only inhibiting GPX4 included pranlukast sodium hydrate, lusutrombopag, brilanestrant, simeprevir, grazoprevir (MK-5172), paritaprevir, navitoclax, venetoclax and VU0661013. Two compounds (metamizole sodium and isoniazid sodium methanesulfate) inhibited all three GPXs but not TXNRD1, while 2,3-dimercaptopropanesulfonate, PI4KIII beta inhibitor 3, SCE-2174 and cefotetan sodium inhibited all tested selenoproteins (but not GR)...With this approach, we could indeed identify novel GPX1/GPX2- or GPX4-specific inhibitors, thus presenting a validated pipeline for future identification of specific selenoprotein-targeting agents. Our study also identified GPX1/GPX2, GPX4 and/or TXNRD1 as targets for several previously developed pharmacologically active compounds."

Journal • Oncology • GPX1 • GPX2 • GPX4

Torasemide-induced Vascular Purpura in the Course of Eosinophilic Granulomatosis with Polyangiitis. (PubMed, Acta Dermatovenerol Croat) - "She was on a constant regimen of oral rosuvastatin 5 mg per day, spironolactone 50 mg per day, metoprolol 150 mg per day, inhaled formoterol 12 μg per day, and ipratropium bromide 20 μg per day...The patient was commenced on prednisone at a dose of 0.5 mg per kg of body weight daily and mycophenolate mofetil at a daily dose of 2 g. The antihypertensive therapy was modified, and torasemide was replaced by spironolactone 25 mg per day...The strongest association with the occurrence of EGPA was found with the use of leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast), although they are commonly used in the treatment of asthma, which is paradoxically one of the complications of the syndrome (13)...A coexistence of several disorders (asthma, nasal polyps, symptoms of peripheral neuropathy) in our patient suggest EGPA could have developed in her years before oral intake of torasemide. The sudden onset of skin symptoms shows torasemide to be possible..."

Journal • Allergic Rhinitis • Asthma • Cardiovascular • Coronary Artery Disease • Dermatology • Eosinophilia • Eosinophilic Granulomatosis With Polyangiitis • Glomerulonephritis • Heart Failure • Hematological Disorders • Hypertension • Immunology • Inflammation • Langerhans Cell Histiocytosis • Lupus Nephritis • Nasal Polyps • Nephrology • Otorhinolaryngology • Pain • Peripheral Neuropathic Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Rheumatology • Sinusitis • Thrombosis • Vasculitis • CRP • MPO

Identification of undefined off-targets of novel drugs and drug combinations with network-based in silico modeling and in vitro validation in hepatocellular carcinoma (EACR 2022) - "Results and Discussions Amrinone, Thalidomide, Chloroquine, Sunitinib, Pranlukast, Pseudoephedrine, Brigatinib, Lenvatinib, and Regorafenib were ranked as the first nine potent drugs. Furthermore, combinations of Brigatinib with Amrinone, Sunitinib or Regorafenib, and Sunitinib with Pseudoephedrine or Chloroquine had synergistic effects on HCC cells. Conclusion Our results have shown that our network-based in silico model can be exploited for drug repurposing and novel target identification."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • DAXX • HDAC1 • HDAC2 • HDAC4 • RELA

Isolation, Characterization, and Toxicity Study of Stress Degradation Products of Pranlukast Hydrate. (PubMed, Chem Res Toxicol) - "DP1, DP2, DP6, and DP10 were found to be hepatotoxic, mutagenic according to the micronucleus test, and aquatic toxic. We can conclude that the drug should be kept away from the direct exposure of light and the toxicity levels of DP1, DP2, DP6, and DP10 should be reduced below 0.1% to avoid their toxic effect."

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