- Cysteinyl leukotriene receptor 1 is a potent regulator of the endosomal-lysosomal system in the ARPE-19 retinal pigment epithelial cell line. [Journal Article]Traffic. 2023 Jan 27 [Online ahead of print]T
- The endosomal-lysosomal system is central for cell homeostasis and comprises the functions and dynamics of particular organelles including endosomes, lysosomes and autophagosomes. In previous studies, we found that the cysteinyl leukotriene receptor 1 (CysLTR1) regulates autophagy in the retinal pigment epithelial cell line ARPE-19 under basal cellular conditions. However, the underlying mechanis…
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- Searching for Novel Noncovalent Nuclear Export Inhibitors through a Drug Repurposing Approach. [Journal Article]J Med Chem. 2023 Jan 26; 66(2):1574-1582.JM
- Chromosomal region maintenance protein 1 (CRM1) is a validated anticancer drug target, and its covalent inhibitor KPT-330 has been approved for marketing. However, the development of CRM1 inhibitors, especially the noncovalent ones, is still very limited. Drug repurposing is an effective strategy to develop drug leads for new targets. In this work, we virtually screened a library of marketed drug…
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- StatPearls: Leukotriene Receptor Antagonists [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Montelukast and zafirlukast are cysteinyl leukotriene receptor antagonists indicated for the prevention and treatment of chronic asthma. This activity will highlight the mechanism of action, adverse event profile, and monitoring pertinent for members of the interprofessional team in the management of patients with asthma and related conditions with leukotriene receptor antagonists.
- The efficacy of Zafirlukast as a SARS-CoV-2 helicase inhibitor in adult patients with moderate COVID-19 Pneumonia (pilot randomized clinical trial). [Randomized Controlled Trial]
- CONCLUSIONS: Among adult patients hospitalized with COVID-19 pneumonia, the treatment with Zafirlukast, compared to placebo, did not significantly improve symptoms resolution.
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- Increased Risk of Tourette Syndrome with Leukotriene Modifier Use in Children with Allergic Diseases and Asthma: A Nationwide Population-Based Study. [Journal Article]
- (1) Background: Cysteinyl leukotriene receptor antagonists (LTRAs), including montelukast and zafirlukast, are FDA-approved for treating pediatric asthma and allergic diseases. Tourette syndrome (TS), a common neuropsychiatric disorder in children, is associated with allergic diseases and asthma. In this study, we investigated the risk of TS following an LTRA prescription for pediatric allergic d…
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- Cheminformatics Bioprospection of Broad Spectrum Plant Secondary Metabolites Targeting the Spike Proteins of Omicron Variant and Wild-Type SARS-CoV-2. [Journal Article]
- The spike protein (SP) of SARS-CoV-2 (SC-2) is susceptible to high mutation and has contributed to the multiple waves of COVID-19 being experienced. Hence, targeting the SP remains a logical approach in the development of potent therapeutics against SARS-CoV-2. Here, a computational technique was adopted to identify broad-spectrum plant secondary metabolites with indigenous relevance in the manag…
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- Blockade of Platelet CysLT1R Receptor with Zafirlukast Counteracts Platelet Protumoral Action and Prevents Breast Cancer Metastasis to Bone and Lung. [Journal Article]
- Metastases are the main cause of death in cancer patients, and platelets are largely known for their contribution in cancer progression. However, targeting platelets is highly challenging given their paramount function in hemostasis. Using a high-throughput screening and platelet-induced breast tumor cell survival (PITCS) assay as endpoint, we identified the widely used anti-asthmatic drugs and c…
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- Selective Inhibition of the Periodontal Pathogen Porphyromonas gingivalis by Third-Generation Zafirlukast Derivatives. [Journal Article]J Med Chem. 2022 11 10; 65(21):14938-14956.JM
- Periodontal diseases are inflammatory diseases triggered by pathogenic oral bacterial species, such as Porphyromonas gingivalis. Zafirlukast (ZAF) has displayed antibacterial activity against P. gingivalis. Herein, we report the design, synthesis, and selective antibacterial activity of 14 novel third-generation ZAF derivatives. Two second-generation ZAF derivatives were tested as they were not p…
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- Torasemide-induced Vascular Purpura in the Course of Eosinophilic Granulomatosis with Polyangiitis. [Case Reports]Acta Dermatovenerol Croat. 2022 Sep; 30(2):116-118.AD
- Torasemide is a loop diuretic with a molecule that is chemically similar to the sulphonamides described as eosinophilic granulomatosis with polyangiitis (EGPA) triggering drugs. The presented case is probably the first description of torasemide-induced vascular purpura in the course of EGPA. Any diagnosis of vasculitis should be followed by an identification of drugs that may aggravate the diseas…
- Antagonism of cysteinyl leukotriene receptors by zafirlukast modulated acute inflammatory reaction in tilapia, Oreochromis niloticus. [Journal Article]Fish Shellfish Immunol. 2022 Nov; 130:323-331.FS
- To identify activation pathways and effector mechanisms of innate immunity in fish has become relevant for the sanitary management of intensive fish farming. However, little is known about the blocking of cysteinyl leukotrienes receptors (CysLTRs) and their effects in teleost fish. Our study evaluated the anti-inflammatory effect of 250 and 500 μg zafirlukast (antagonist of CysLTRs)/kg b.w., admi…
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- Cysteinyl-maresin 3 inhibits IL-13 induced airway hyperresponsiveness through alternative activation of the CysLT1 receptor. [Journal Article]Eur J Pharmacol. 2022 Nov 05; 934:175257.EJ
- CONCLUSIONS: MCTR3, but not LTD4, decreased the IL-13-induced airway hyperresponsiveness by activation of the CysLT1 receptor. The distinct actions of the two lipid mediators on the CysLT1 receptor suggest an alternative signalling pathway appearing under inflammatory conditions, where this new action of MCTR3 implicates potential to inhibit airway hyperresponsiveness in asthma.
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- Lupeol and pristimerin do not inhibit activation of the human sperm CatSper Ca(2+)-channel. [Journal Article]
- Opposing findings have been published on the regulation of the sperm-specific Ca 2+ channel CatSper (cation channel of sperm) in human sperm cells by the plant triterpenoids lupeol and pristimerin. While the original study on this topic found these triterpenoids to act as potent inhibitors of human CatSper, subsequent studies have failed to replicate such an inhibitory effect. It has been suggest…
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- Drug-Initiated Activity Metabolomics Identifies Myristoylglycine as a Potent Endogenous Metabolite for Human Brown Fat Differentiation. [Journal Article]
- Worldwide, obesity rates have doubled since the 1980s and in the USA alone, almost 40% of adults are obese, which is closely associated with a myriad of metabolic diseases such as type 2 diabetes and arteriosclerosis. Obesity is derived from an imbalance between energy intake and consumption, therefore balancing energy homeostasis is an attractive target for metabolic diseases. One therapeutic ap…
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- Comparison of Cromolyn Sodium, Montelukast, and Zafirlukast Prophylaxis for Capsular Contracture. [Journal Article]Plast Reconstr Surg. 2022 11 01; 150(5):1005e-1014e.PR
- CONCLUSIONS: Cromolyn sodium appears to inhibit capsular contracture more efficiently than montelukast and zafirlukast. This report may be a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture.
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- A Disproportionality Analysis of Drug-Drug Interactions of Tizanidine and CYP1A2 Inhibitors from the FDA Adverse Event Reporting System (FAERS). [Journal Article]
- CONCLUSIONS: Reports involving tizanidine and a CYP1A2 inhibitor have higher odds of reporting hypotension. This study suggests that concurrent use of tizanidine with CYP1A2 inhibitors may lead to serious health consequences associated with low blood pressure such as falls and fractures.
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- Small scale in vitro method to determine a potential bioequivalent equilibrium solubility range for fed human intestinal fluid. [Journal Article]Eur J Pharm Biopharm. 2022 Aug; 177:126-134.EJ
- Intestinal drug solubility is a key parameter controlling oral absorption but varies both intra and inter individuals and between the fasted and fed states, with food intake known to alter the bioavailability of many compounds. Intestinal solubility can be measured in vitro either using sampled fed human intestinal fluid (FeHIF) or simulated fed intestinal fluid (SIF) but neither approach is opti…
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- StatPearls: Zafirlukast [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Zafirlukast is a medication used in the management and treatment of chronic asthma. It is in the leukotriene receptor antagonist class. This activity reviews the indications, action, and contraindications for zafirlukast as an agent in the management and prophylaxis of chronic asthma. This activity will highlight the mechanism of action, adverse event profile, and other vital factors pertinent to…
- Low-Frequency Raman Spectroscopy as an Avenue to Determine the Transition Temperature of β- and γ-Relaxation in Pharmaceutical Glasses. [Journal Article]Anal Chem. 2022 06 14; 94(23):8241-8248.AC
- In an earlier investigation, low-frequency Raman (LFR) spectroscopy was shown to detect the transition temperature of the β-relaxation (Tβ) in both amorphous celecoxib and various celecoxib amorphous solid dispersions [Be̅rziņš, K. Mol. Pharmaceutics 2021, 18(10), 3882-3893]. In this study, we further investigated the application of this technique to determine Tβ, an important parameter for estim…
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- Structured solubility behaviour in bioequivalent fasted simulated intestinal fluids. [Journal Article]Eur J Pharm Biopharm. 2022 Jul; 176:108-121.EJ
- Drug solubility in intestinal fluid is a key parameter controlling absorption after the administration of a solid oral dosage form. To measure solubility in vitro simulated intestinal fluids have been developed, but there are multiple recipes and the optimum is unknown. This situation creates difficulties during drug discovery and development research. A recent study characterised sampled fasted …
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- Choline-Amino Acid-Derived Bio-ionic Liquids for Solubility Enhancement of Zafirlukast. [Journal Article]
- This study investigated the application of bio-ionic liquids (ILs) prepared from choline as cation and amino acid as anion for solubility enhancement of poorly water-soluble drug, Zafirlukast (ZFL). Herein, the solubility of ZFL in water and mixtures of water and ILs was assessed using UV spectroscopy at two temperature points 25°C and 37°C with increasing concentrations of IL. ZFL solubility was…
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- Zafirlukast Induces VHL- and HIF-2α-Dependent Oxidative Cell Death in 786-O Clear Cell Renal Carcinoma Cells. [Journal Article]
- Mutations in the Von Hippel-Lindau (VHL) gene are the driving force in many forms of clear cell renal cell carcinoma (ccRCC) and promote hypoxia-inducible factor (HIF)-dependent tumor proliferation, metastasis and angiogenesis. Despite the progress that has already been made, ccRCC generally remain resistant to conventional therapies and ccRCC patients suffer from metastasis and acquired resistan…
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- Zafirlukast inhibits the growth of lung adenocarcinoma via inhibiting TMEM16A channel activity. [Journal Article]
- Lung cancer has the highest mortality among cancers worldwide due to its high incidence and lack of the effective cures. We have previously demonstrated that the membrane ion channel TMEM16A is a potential drug target for the treatment of lung adenocarcinoma and have identified a pocket of inhibitor binding that provides the basis for screening promising new inhibitors. However, conventional drug…
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- Drug repurposing for identification of potential spike inhibitors for SARS-CoV-2 using molecular docking and molecular dynamics simulations. [Journal Article]
- For the last two years, the COVID-19 pandemic has continued to bring consternation on most of the world. According to recent WHO estimates, there have been more than 5.6 million deaths worldwide. The virus continues to evolve all over the world, thus requiring both vigilance and the necessity to find and develop a variety of therapeutic treatments, including the identification of specific antivir…
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- In Silico Drug Repurposing Approach: Investigation of Mycobacterium tuberculosis FadD32 Targeted by FDA-Approved Drugs. [Journal Article]
- Background: Despite the enormous efforts made towards combating tuberculosis (TB), the disease remains a major global threat. Hence, new drugs with novel mechanisms against TB are urgently needed. Fatty acid degradation protein D32 (FadD32) has been identified as a promising drug target against TB, the protein is required for the biosynthesis of mycolic acids, hence, essential for the growth and …
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- A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC). [Review]
- Newly emerging roles of LRRC8 volume-regulated anion channels (VRAC) raise important questions about the therapeutic potential of VRAC in the treatment of epilepsy, type 2 diabetes, and other human diseases. A critical barrier to evaluating whether VRAC represents a viable drug target is the lack of potent and specific small-molecule inhibitors and activators of the channel. Here we review recent…
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- Leukotriene Antagonists in Dermatology. [Journal Article]
- Leukotriene antagonists constitute an important group of drugs in the therapeutic armamentarium of all dermatologists. It has been quite valuable in the management of various types of urticaria and atopic dermatitis. Recently, the role of zileuton in the management of acne has been elaborated, and in the near future it could be used as a first-line agent for the same, thereby preventing adverse e…
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- Cysteinyl Leukotriene Pathway and Cancer. [Review]
- Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl leukotriene (CysLT) pathway is involved in several signal pathways, having various functions in different tissues. We summarized major findings of studie…
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- Chronobiological activity of cysteinyl leukotriene receptor 1 during basal and induced autophagy in the ARPE-19 retinal pigment epithelial cell line. [Journal Article]
- Autophagy is an important cellular mechanism for maintaining cellular homeostasis, and its impairment correlates highly with age and age-related diseases. Retinal pigment epithelial (RPE) cells of the eye represent a crucial model for studying autophagy, as RPE functions and integrity are highly dependent on an efficient autophagic process. Cysteinyl leukotriene receptor 1 (CysLTR1) acts in immun…
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- Leukotrienes Are Dispensable for Vaginal Neutrophil Recruitment as Part of the Immunopathological Response During Experimental Vulvovaginal Candidiasis. [Journal Article]
- Recruitment of polymorphonuclear neutrophils (PMNs) into the vaginal lumen is the hallmark of an acute immunopathologic inflammatory response during vulvovaginal candidiasis (VVC) caused by Candida albicans. Recurrent VVC (RVVC) remains a chronic health burden in affected women worldwide despite the use of antifungal therapy. Based on the role leukotrienes (LTs) play in promoting inflammation, le…
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- Combination of eudragit EPO with poloxamers for improved solubility and dissolution of Zafirlukast: An evaluation of solid dispersion formulations. [Journal Article]Pak J Pharm Sci. 2021 Sep; 34(5(Supplementary)):1923-1928.PJ
- This study investigated the effect of solid dispersions (SD) on solubility and release of Zafirlukast (ZA) by physical mixture (PM), solvent evaporation (SE) and kneading method (KM) with Eudragit EPO (EPO) as binary component and Poloxamer 188 (P188) and Poloxamer 407 (P407) as ternary components. The binary and ternary systems caused an increase of 322 folds and 356 folds in aqueous solubility …