Joicela (lumiracoxib) / Novartis - LARVOL DELTA

Lipid Raft Membrane Interactivity Correlating with Cyclooxygenase-2 Selectivity of Non-Steroidal Anti-Inflammatory Drugs. (PubMed, Membranes (Basel)) - "Conventional NSAIDs (diclofenac, ibuprofen, indomethacin, aspirin, and flurbiprofen) and Coxibs (lumiracoxib, etoricoxib, celecoxib, valdecoxib, and rofecoxib) decreased membrane fluidity, whereas Oxicams (meloxicam, piroxicam, tenoxicam, and lornoxicam) increased. Under inflammatory acidic conditions, the lipid raft membrane interactivity of NSAIDs was more likely to correlate with cyclooxygenase-2 selectivity than the reference membrane interactivity. It is hypothesized that NSAIDs may interact with lipid raft membranes to induce membrane fluidity changes with the potency corresponding to cyclooxygenase-2 inhibition, disrupting the structural and functional integrity of lipid rafts to affect the activity of cyclooxygenase-2 localized in lipid rafts, resulting in cyclooxygenase-2 selective inhibition."

Journal

mPGES inhibitor induces a switch to prostacyclin in human alveolar epithelial cells and lung fibroblasts (ERS 2025) - " hAELvi and HFL-1 were pretreated with the selective COX-2 inhibitor lumiracoxib (0.01-1 µM) or the mPGES-1 inhibitor 30118 (0.01-1 µM) before exposure to hypoxia (1% O 2 ) and/or TGF-β1 (10 ng/mL) for 24 hours... Our data indicates that PGE 2 and PGI 2 can be synthesised in high amounts in alveolar compartments and that the mPGES-1 inhibitor cause a switch to prostacyclin synthesis."

Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL6 • TGFB1

Thromboxane A2, not prostaglandin D2, drives the prostanoid-mediated component of mast cell-induced constriction in human small airways (ERS 2025) - "The remaining contraction was abolished (p<0.05) by unselective COX inhibitor indomethacin, selective COX-1 inhibitor FR 122,047, or TP receptor antagonist SQ-29,548, whereas COX-2 inhibitor lumiracoxib had no effect (E max: 57±7%). The selective thromboxane (TX) A synthase inhibitor ozagrel prevented the prostanoid component of the contraction (p<0.05), whereas the prostaglandin (PG) D synthase inhibitor PPCA unexpectedly increased it (E max: 67±7%, p<0.05)...TXA 2 rather than PGD 2 mediates the contractile prostanoid component. The findings may explain why PGD 2 antagonism failed in treatment of asthma."

Asthma • Immunology • Respiratory Diseases

The STUB1-TPIT axis regulates the secretion of adrenocorticotrophic hormone in cushing disease. (PubMed, J Transl Med) - "STUB1 is a promising therapeutic target for CD and drugs targeting the STUB1-TPIT complex may provide a potential treatment approach."

Journal • Cushing’s Disease • Endocrine Disorders • POMC-null Obesity • Targeted Protein Degradation • STUB1

The role of the cyclooxygenase-2 pathway in tissue ischemia and revascularization following skeletal muscle injury induced by bothropic snake venom. (PubMed, Microvasc Res) - "Mice were injected with Bav into the gastrocnemius muscle and treated with lumiracoxib, a selective COX-2 inhibitor, 30 min, 2 days, and 6 days post-Bav injection...In conclusion, the COX-2 pathway is essential to decrease the high grade of ischemia caused by acute injury induced by Bav. However, the decrease of activity in the COX-2 pathway in the first stages of revascularization contributes to the elevated production of key pro-angiogenic mediators that up-regulate the restoration of microvasculature and blood flow in muscle tissue injured by botropic venoms."

Journal • Cardiovascular • CD31 • MMP10 • MMP13 • MMP9 • PECAM1 • PTGS2

Renal effects of selective cyclooxygenase-2 inhibitor anti-inflammatory drugs: A systematic review and meta-analysis. (PubMed, Explor Res Clin Soc Pharm) - "Randomized controlled trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) were searched in PubMed, Embase, Scopus and other sources up to March 2024. Coxibs likely increase the renal adverse effects, including hypertension and edema. Awareness about the renal risks of coxibs should be increased, mainly in high-risk patient."

Journal • Retrospective data • Review • Cardiovascular • Gastrointestinal Disorder • Hypertension • Nephrology

Obesity Inhibits Alveolar Macrophage Responses to Pseudomonas aeruginosa Pneumonia via Upregulation of Prostaglandin E2 in Male, but Not Female, Mice. (PubMed, J Immunol) - "Treatment with lumiracoxib-conjugated nanocarriers targeting alveolar macrophages improves bacterial phagocytosis and clearance in both ND and HFD male animals. Our study highlights that obesity leads to worse morbidity during bacterial pneumonia in male mice because of elevated PGE2. In addition, we uncover a sex difference in both obesity and infection, because females produce high basal PGE2 but because of a failure to signal via cAMP do not display impaired phagocytosis."

Journal • Preclinical • Genetic Disorders • Infectious Disease • Obesity • Pneumonia • Respiratory Diseases

Solubility of lumiracoxib in supercritical carbon dioxide. (PubMed, Sci Rep) - "Moreover, the measured solubility data of these two drugs are correlated with density-based semi-empirical correlations namely Bartle et al., Mendez-Santiago-Teja, Kumar and Johnstone, Chrastil and modified Chrastil models with an average absolute relative deviation of 10.7%, 9.5%, 9.8%, 7.8%, and 8.7% respectively for lumiracoxib. According to these findings, it is obvious that all of the examined models are rather accurate and there is no superiority between these models for both examined drugs although the Chrastil model is slightly better in the overall view."

Journal

Efficacy and safety of simple analgesics for acute treatment of episodic tension-type headache in adults: a network meta-analysis. (PubMed, Ann Med) - "For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence)."

Clinical • Journal • Retrospective data • Review • Pain

Bioactivity of dihydropyrimidinone derivatives as inhibitors of cyclooxygenase-2 (COX-2): an in silico approach. (PubMed, RSC Adv) - "Molecular docking served as the initial step of selection, based on the comparison of grid score, docking pose, and interactions with those of lumiracoxib (LUR) as the original ligand of COX-2...The results of the MD simulation indicated that RDUE2 and SDT29 interacted stably with amino acid residues on the active site of COX-2. The estimation of binding free energy indicated that SDT29 exhibited an inhibitory activity comparable to that of LUR, whereas RDUE2 showed a lower inhibitory activity than that of SDT29 and LUR."

Journal • Inflammation • PTGS2

Unveiling the therapeutic promise of natural products in alleviating drug-induced liver injury: Present advancements and future prospects. (PubMed, Phytother Res) - "From 1997 to 2016, eight drugs, including troglitazone, nefazodone, and lumiracoxib, were removed from the market due to their liver-damaging effects, which can cause diseases. To advance DILI management, it is crucial to conduct well-designed randomized clinical trials to evaluate natural products' efficacy and develop new molecules clinically. However, natural products are a promising solution for remedying drug-induced hepatotoxicity and lowering the risk of DILI."

Clinical • Journal • Review • Hepatology • Infectious Disease • Inflammation • Liver Failure • Metabolic Disorders • Respiratory Diseases • Tuberculosis

Molecular insights in repurposing selective COX-2 inhibitor celecoxib against matrix metalloproteinases in potentiating delayed wound healing: a molecular docking and MMPB/SA based analysis of molecular dynamic simulations. (PubMed, J Biomol Struct Dyn) - "We considered five selective COX-2 inhibitors (celecoxib, etoricoxib, lumiracoxib, rofecoxib and valdecoxib) for our study against MMPs. The in silico analysis of the secondary structures showed that the celecoxib binding conformation maintains relatively stable along the simulation trajectories. These findings provide some key clues regarding the accommodation of celecoxib in the substrate binding S1' pocket and also provide structural insights and challenges in repurposing drugs as new MMP inhibitors with anti-inflammatory and anti-inflammatory wound-healing properties.Communicated by Ramaswamy H. Sarma."

Journal • Fibrosis • Inflammation • MMP2 • MMP9

The early inhibition of the COX-2 pathway in viperid phospholipase A-induced skeletal muscle myotoxicity accelerates the tissue regeneration. (PubMed, Toxicol Appl Pharmacol) - "The expression of Pax7 and myogenin were increased, indicating a great capacity for storing satellite cells and advanced mature state of tissue. Our data reveals a distinct role of COX-2-derived products during muscle degeneration and regeneration, in which early administration of lumiracoxib was a therapeutic strategy to modulate the effects of prostaglandins, providing a breakthrough in muscle tissue regeneration induced by a myotoxic PLA"

Journal • Fibrosis • Immunology • Myogenin • PAX7

Cell-Type Specific Induction of Cyclo-Oxygenase-2 in Layer II/III Prefrontal Cortical Neurons Mediates Stress-Induced Anxiety Phenotypes in Mice (ACNP 2022) - "Using a pharmacological approach, we found that systemic lumiracoxib, a selective Ptgs2-inhibitor, led to a significant reduction in fear expression (2-way ANOVA, Drug effect, p=0.03)... Together these findings suggest that Ptgs2 is expressed in a dynamic, cell-type specific way in Layer II/III Penk+ neurons in mPFC, and that its role in prostaglandin and /or endocannabinoid regulation within these neurons may be an important mediator of stress-related anxiety behavior."

Preclinical • Behavior Disorders • Mental Retardation • Mood Disorders • Psychiatry • BDNF • PACERR • PTGS2

Safety data and withdrawal of hepatotoxic drugs. (PubMed, Therapie) - "Several relevant factors may contribute to an inadequate risk management leading to the discontinuation of the drugs. Preclinical safety data are not sufficient to allow early prediction of DILI in humans and post-marketing safety monitoring and signal detection still should be used to identify potential serious cases of DILI. However, it seems that changes in Pharmacovigilance legislation with a closer management of drug safety may have contributed to the improvement of the risk minimization."

Clinical • Journal • Hepatology • Liver Failure

New horizons in the roles and associations of COX-2 and novel natural inhibitors in cardiovascular diseases. (PubMed, Mol Med) - "Coxibs, including celecoxib, valdecoxib, etoricoxib, parecoxib, lumiracoxib, and rofecoxib, are selective cyclooxygenase-2 (COX-2) inhibitors used to treat osteoarthritis and rheumatoid arthritis...Interestingly, nabumetone, flurbiprofen axetil, piketoprofen-amide, and nepafenac are ester prodrugs that inhibit COX-2. The combination of galangin-like flavonol compounds with these prodrug metabolites may lead to the development of novel COX-2 inhibitors. This review focuses on the most compelling evidence regarding the role and mechanism of COX-2 in cardiovascular diseases and demonstrates that quercetin-like compounds exert potential cardioprotective effects by serving as cofactors of COX-2."

Journal • Review • Cardiovascular • Immunology • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology

Catalytically active phospholipase A myotoxin from Crotalus durissus terrificus induces proliferation and differentiation of myoblasts dependent on prostaglandins produced by both COX-1 and COX-2 pathways. (PubMed, Int J Biol Macromol) - "Myoblast C2C12 were cultured in proliferation or commitment protocols and incubated with CB followed by lumiracoxib (selective COX-2 inhibitor) or valeryl salicylate (selective COX-1 inhibitor) and subjected to analysis of PG release, cell proliferation and activation of myogenic regulatory factors (MRFs)...Our findings evidence the role of COX-1- and COX-2-derived PGs in modulating CB-induced activation of MRFs. This study contributes to the knowledge that CB promote early myogenic events via regulatory mechanisms on PG-dependent COX pathways, showing new concepts about the effect of sPLA-IIA in skeletal muscle repair."

Journal • Myogenin • PTGS2

Prostaglandin D inhibits mediator release and antigen induced bronchoconstriction in the Guinea pig trachea by activation of DP receptors. (PubMed, Eur J Pharmacol) - "This release was eliminated by unselective COX inhibition (indomethacin) whereas selective inhibition of COX-2 (lumiracoxib) did not inhibit release of PGD or thromboxanes. In the guinea pig trachea, endogenous PGD is generated via COX-1 and mediates an inhibitory effect of the antigen-induced bronchoconstriction via DP receptors inhibiting mast cell release of bronchoconstrictive mediators. Removal of this protective function by COX-inhibition results in increased release of mast cell mediators and enhanced bronchoconstriction."

Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A validated UHPLC-MS/MS method for simultaneous determination of lumiracoxib and its hydroxylation and acyl glucuronidation metabolites in rat plasma: Application to a pharmacokinetic study. (PubMed, J Pharm Biomed Anal) - "All the analytes were demonstrated to be stable under the tested storage and processing conditions. The validated LC-MS/MS method has been successfully applied to the pharmacokinetic study of lumiracoxib and its metabolites in the rats after orally administered with lumiracoxib."

Journal • PK/PD data • Preclinical

Grabbing GRB2: The use of liposome-incorporated Grb2 antisense oligonucleotides as a novel therapy in gynecologic malignancies (AACR 2018) - "There was an eighty-six percent decrease in tumor burden (p<0.05), and multinodular burden (p<0.01) in the combination prexigebersen/paclitaxel group compared to control. Prexigebersen shows promising preclinical efficacy and may be a novel therapeutic strategy in gynecologic malignancies."

Leukemia • Ovarian Cancer

Cyclooxygenase-2 inhibition prevents stress induced amygdala activation and anxiety-like behavior. (PubMed, Brain Behav Immun) - "Here, we examined the effects of pharmacological inhibition of COX-2 with the highly selective inhibitor Lumiracoxib (LMX) on anxiety-like behavior and in vivo basolateral amygdala (BLA) neural activity in response to acute restraint stress exposure...In addition, in vivo fiber photometry studies showed that acute stress increased calcium transients and the predicted action potential frequency of BLA neurons, which was also normalized by acute LMX pretreatment. These findings indicate pharmacological inhibition of COX-2 can prevent acute stress-induced increase in BLA cellular activity and anxiety-like behavior and provides insights into the neural mechanisms by which COX-2 inhibition could affect anxiety domain symptoms in patients with affective disorders."

Journal • CNS Disorders • Depression • Mood Disorders

Evaluation of a human in vitro skin test for predicting drug hypersensitivity reactions. (PubMed, Toxicol Appl Pharmacol) - "Responses in the skin explant test for 12 LMW drugs associated with T cell-mediated hypersensitivity in the clinic (abacavir, amoxicillin, carbamazepine, diclofenac, lamotrigine, lapatinib, lumiracoxib, nevirapine, ofloxacin, phenytoin, propranolol, sulfamethoxazole) were compared with responses for 5 drugs with few/no reports of T cell-mediated hypersensitivity reactions (acetaminophen, cimetidine, flecainide, metformin, verapamil). The T cell proliferation assay showed a correlation of r = 0.60 (p < .01) and the IFNγ assay r = 0.51 (p < .04). The data suggest that the skin explant model could be a useful tool to predict the potential of LMW drugs to induce DHRs."

Journal • Allergy • Immunology

Bioactivation of Lumiracoxib in Human Liver Microsomes: Formation of GSH- and Amino Adducts Through Acyl Glucuronide. (PubMed, Drug Test Anal) - "In addition to reaction with GSH, the formed 1-O-acylglucuronides were chemically unstable (T = 1.5 h in phosphate buffer) and rearranged to 2-, 3-, and/or 4-isomers, which further underwent ring-openning to form aldehyde derivatives and then reacted with NAL to yield Schiff bases derivatives (M5-M8). The present study provides a clear bioactivation profile of lumiracoxib through acyl glucuronidation, which would be one of the mechanisms attributed to the liver injury caused by lumiracoxib."

Journal

The association between nonsteroidal anti-inflammatory drugs and skin cancer: Different responses in American and European populations. (PubMed, Pharmacol Res) - "The use of NSAIDs might reduce the risk of SC, but many factors including study population, drug subtype, and disease subclass affect the significance of the association."

Clinical • Journal

Metabolic targeting synergizes with MAPK inhibition and delays drug resistance in melanoma. (PubMed, Cancer Lett) - "In combination with the RAF inhibitor vemurafenib strong synergism was observed: Diclofenac as well as lumiracoxib increased the anti-glycolytic impact of vemurafenib and prevented RAF-inhibitor induced metabolic reprogramming towards OXPHOS. Furthermore the addition of NSAIDs delayed the onset of RAF inhibitor resistance, most likely by counteracting the upregulation of MITF. Our data suggest that selected NSAIDs could be a promising combination partner for MAPK pathway inhibitors in the treatment of BRAF mutated melanomas."

Journal