rofecoxib (TRM-201) / Tremeau Pharma - LARVOL DELTA

A Rofecoxib-Derived Theranostic Probe and Its Combination With PD-1 Inhibitor for High-Efficiency Cancer Therapy. (PubMed, Arch Pharm (Weinheim)) - "Compound 2 involves activating fluorescence by targeting tumor markers COX-2 as well as enhancing therapeutic efficacy. We believe this approach could provide insights for advancing cancer diagnosis and treatment technologies."

IO biomarker • Journal • Oncology • PD-L1

From chronic gastritis to gastric cancer: Mendelian randomisation and multi-omics interrogation of leukaemia inhibitory factor receptor (LIFR), hepatocyte growth factor (HGF), serine protease inhibitor E1 (SERPINE1) and interleukin-10 receptor subunit beta (IL10RB). (PubMed, Int J Biol Macromol) - "Collectively, these data define a molecular continuum from chronic gastritis to GC and highlight LIFR, IL10RB, SERPINE1 and HGF as pivotal biological macromolecules and candidate therapeutic targets. The repurposing potential of anti-inflammatory agents, particularly rofecoxib and nabumetone, suggests a feasible strategy to intercept the gastritis-carcinoma sequence."

Journal • Gastric Cancer • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • IL10 • LIFR • SERPINE1

Drug exposure before and during pregnancy and thromboembolic events: a disproportionality analysis from the FAERS database. (PubMed, Int J Surg) - "Drawing on the FAERS database, we have provided a list of drugs with risk signals for PTEs in this exploratory study. Our findings highlight the importance of considering both before and during-pregnancy drug exposures when assessing thromboembolism risk. More well-designed studies are warranted for drugs whose association with PTEs is not fully understood."

Journal • Cardiovascular

Synthesis, structural elucidation, and molecular docking of diclofenac-derived hydrazone metal complexes with anti-inflammatory and anticancer potential. (PubMed, Sci Rep) - "The HDN ligand exhibited potent COX-2 inhibition (IC₅₀ = 0.06 µM) with a selectivity index (SI) of 174.5, outperforming diclofenac sodium (SI = 4.52) and indomethacin (SI = 1.25), and approaching rofecoxib (SI = 725). The Cu(II) and Gd(III) complexes showed strong cytotoxicity in MTT assays against MCF-7 (IC₅₀ = 0.65 and 0.80 µM) and HepG-2 (IC₅₀ = 1.00 and 2.47 µM) cell lines, significantly surpassing the HDN ligand and standard drugs such as 5-fluorouracil (IC₅₀ = 3.95 µM, MCF-7) and cisplatin (IC₅₀ = 15.24 µM, MCF-7)...The present results provide a preclinical proof-of-concept for diclofenac-derived Schiff base metal complexes as dual anti-inflammatory and anticancer agents. However, their therapeutic potential remains to be validated through stability, mechanistic, and in vivo investigations."

Journal • Oncology

Cyclooxygenase-2 inhibition improves hypercholesterolemia-induced cardiac dysfunction. (PubMed, Biomed Pharmacother) - "Cdc42ep4, Cox5, and Cxcl9 genes were also counter-regulated following rofecoxib treatment compared to HC-induced changes. This is the first demonstration that rofecoxib improves HC-induced cardiac dysfunction, with the mechanism involving changes in the gene expression profile, including some key regulators of rofecoxib action."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • Reperfusion Injury • CXCL9 • MIR27A • MIR30D

Kidney Safety of Nonsteroidal Anti-Inflammatory Drugs in Patients with Arthritis: A Network Meta-Analysis (KIDNEY WEEK 2025) - "NSAIDs evaluated were naproxen (n=17,185), ibuprofen (n=28,531), celecoxib (n=37,843), oral diclofenac (n=6,060), rofecoxib (n=804), nabumetone (n=15), valdecoxib (n=544), and amtolmetin guacil (n=30)...Conclusion Rofecoxib, naproxen, and diclofenac are associated with a higher incidence of renal AEs, edema, and HTN compared with placebo, respectively. Physicians should weigh renal safety when prescribing NSAIDs for arthritis."

Retrospective data • Immunology • Osteoarthritis • Rheumatoid Arthritis • Rheumatology

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

Primary Stabbing Headache: A Narrative Review of an Underrecognized Pain Syndrome (IHC 2025) - "Pharmacological treatments identified across studies included COX-2 inhibitors, indomethacin, paracetamol, celecoxib, melatonin, gabapentin, nifedipine, and rofecoxib. Despite being a benign and self-limiting headache disorder, PSH still presents diagnostic challenges due to its atypical presentation and lack of specific biomarkers. Further clinical and pathophysiological research is warranted to improve diagnostic precision and to evaluate the efficacy and safety of currently used pharmacological interventions."

Review • CNS Disorders • Migraine

Comprehensive Analysis of Gastrointestinal Injury Induced by Nonsteroidal Anti-Inflammatory Drugs Using Data from FDA Adverse Event Reporting System Database. (PubMed, Pharmaceuticals (Basel)) - "Cyclooxygenase-2 (COX-2) selective NSAIDs (e.g., celecoxib, rofecoxib) were associated with a lower incidence but greater severity, primarily in the upper GI tract. Conversely, nonselective NSAIDs (e.g., acetylsalicylic acid, lornoxicam) showed higher incidence rates, though the events were generally milder. In our dataset, acetylsalicylic acid had the highest incidence, whereas meloxicam showed the highest severity... NSAIDs differ significantly in their gastrointestinal adverse event profiles, attributable to COX selectivity. When selecting an NSAID, both the likelihood and the nature of potential GI harm should be considered."

Adverse events • Journal • Gastroenterology • Gastrointestinal Disorder

Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin. (PubMed, Biomolecules) - "The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (-16.528 kcal/mol), Tophit2 (-10.879 kcal/mol), Tophit3 (-9.760 kcal/mol), Tophit4 (-9.752 kcal/mol), Tophit5 (-8.742 kcal/mol), and Tophit6 (-8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (-7.305 kcal/mol)...ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

Assessment of drug induced hyperuricemia and gout risk using the FDA adverse event reporting system. (PubMed, Sci Rep) - "Among the hyperuricemia-related reports, telaprevir was the most frequently implicated drug, whereas lenalidomide ranked highest in the gout-related reports...Specifically, peginterferon alfa-2b was found to be an independent risk factor for drug-induced hyperuricemia, while 20 drugs-including pegloticase, febuxostat, allopurinol, rofecoxib, and furosemide-were identified as independent risk factors for drug-induced gout...Furthermore, key independent risk factors-including sex, age, and specific drugs-were identified through machine learning and multivariate analysis. These findings provide valuable insights for pharmacovigilance and clinical medication management."

Adverse events • Journal • Gout • Inflammatory Arthritis • Rheumatology

Assessment of the molecular mechanisms of drug-induced hidden cardiotoxicity by a multi-omics approach: The example of rofecoxib. (PubMed, Br J Pharmacol) - "This is the first demonstration that multi-omics characterisation can reveal underlying regulatory pathways of hidden cardiotoxicity. Importantly, our study shows that transcriptomics gives limited information on the hidden cardiotoxic effects of rofecoxib, which are mainly mediated by changes in posttranslational modifications and protein expression. These changes, among other mechanisms, may disturb the cardiac calcium handling, which could explain the fatal arrhythmias following ischaemia/reperfusion observed with rofecoxib."

Journal • Cardiovascular • Reperfusion Injury • Targeted Protein Degradation

Carpal Tunnel Syndrome Attributed to Medication Use: A Pharmacovigilance Study. (PubMed, Cureus) - "Several drugs were disproportionately associated with CTS in the FAERS database, including enzyme replacement therapies (ERTs), aromatase inhibitors, bisphosphonates, growth hormone (GH)-releasing factor analogs, GHB, rofecoxib, and tafamidis. These findings highlight the critical need for increased vigilance and monitoring of new-onset or worsening CTS in high-risk populations prescribed the aforementioned medications. Clinicians should carefully scrutinize pharmacological history when evaluating patients in this context."

Adverse events • Journal • Musculoskeletal Pain • Pain

The role of anti-inflammatory drugs in pain management and osseointegration after orthodontic micro implant brace surgery. (PubMed, Pak J Pharm Sci) - "This study systematically compared the efficacy of four nonsteroidal anti-inflammatory drugs (NSAIDs) including a placebo, ibuprofen, diclofenac potassium, and rofecoxib-in managing postoperative pain and their impact on osseointegration following orthodontic micro implant surgery. The ibuprofen group achieved the highest scores in occlusal function, aesthetics, masticatory function and satisfaction with orthodontic treatment. The study establishes a rationale for drug selection in pain management and osseointegration post-orthodontic micro implant surgery, affirming the short-term safety and efficacy of NSAIDs in orthodontic procedures."

Clinical • Journal • Pain • BMP2

Fate-tox: fragment attention transformer for E(3)-equivariant multi-organ toxicity prediction. (PubMed, J Cheminform) - "However, avoiding toxicity of an organ, such as reducing gastrointestinal side effects, may inadvertently lead to toxicity in another organ, as seen in the real case of rofecoxib, which was withdrawn due to increased cardiovascular risks...Additionally, attention visualization aligning with literature contributes to greater transparency in predictive modeling. Our approach has the potential to provide scientists and clinicians with a more interpretable and clinically meaningful tool to assess systemic toxicity, ultimately supporting safer and more informed drug development processes."

Journal • Cardiovascular

Molecular Docking and dynamic simulation analysis of flavonoid derivatives as COX-2 inhibitors. (PubMed, In Silico Pharmacol) - "Binding affinity calculations revealed that several flavonoids exhibited strong interactions with COX-2, with Cudraflavone A showing the highest binding affinity of - 10.19 kcal/mol, surpassing the standard inhibitor Rofecoxib (- 9.4 kcal/mol)...This study provides valuable insights into the potential development of flavonoid-based COX-2 inhibitors for cancer and anti-inflammatory therapeutics. The online version contains supplementary material available at 10.1007/s40203-025-00349-x."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Drug-Related Hypertension: A Disproportionality Analysis Leveraging the FDA Adverse Event Reporting System. (PubMed, J Clin Hypertens (Greenwich)) - "Some drugs, such as rofecoxib, lenvatinib, and celecoxib, were found to appear on both the frequency and signal strength lists. These results contribute to a more comprehensive understanding of the cardiovascular safety profiles of pharmacological agents, suggesting the necessity of blood pressure monitoring following administration."

Adverse events • Journal • Cardiovascular • Hypertension

Interventions to Treat Sleep Disturbances After Total Hip or Knee Arthroplasty: A Systematic Review (AAOS 2025) - "Zolpidem, melatonin, pregabalin, gabapentin, long-acting morphine, preoperative methylprednisolone, rofecoxib, electroacupuncture, meditation, and chilled intraoperative irrigation with epinephri ne were found to be efficacious interventions in improving sleep quality at least 1 day postoperatively. Of those, 10mg zolpidem administered 2 days preoperatively and 5 days postoperatively, 125mg of intravenous methylprednisolone administered immediately preoperatively, and self-guided meditation performed 2 weeks preoperatively and postoperatively were associated with significant improvements in sleep quality for 2 or more weeks postoperatively. Sleep quality has been demonstrated to be poor in the postoperative period following total joint arthroplasty, leading to increased pain and worse functional outcomes. Interventions which showed long-term improvements in sleep quality, including zolpidem, preoperative methylprednisolone, and meditation, should be considered in all..."

Review • CNS Disorders • Orthopedics • Pain • Sleep Disorder

Leptomonines A and B, two novel rare benzyltetrahydroisoquinoline N-oxides from the aerial parts of Leptopyrum fumarioides as potential COX-2 inhibitors: in vitro and in silico studies. (PubMed, J Nat Med) - "The interactions of these alkaloids with the targets were mainly with the hydrophobic and hydrophilic sites, which are quite similar to rofecoxib...Two new benzyltetrahydroisoquinoline N-oxides were identified as the bioactive constituents of Leptopyrum fumarioides by assessing its anti-inflammatory effects. The findings provide scientific justification to support the traditional application of Leptopyrum fumarioides for treating liver diseases associated with inflammation."

Journal • Preclinical • Hepatology • Inflammation • PTGS2 • TNFA

Pharmaceutical product recall and educated hesitancy towards new drugs and novel vaccines. (PubMed, Int J Risk Saf Med) - "This excess mortality may include adverse effects caused by novel pharmaceutical agents that use gene-code technology.Objective: To examine key pharmaceutical product withdrawals and derive lessons that inform the current use of gene-based COVID-19 vaccines. Selective narrative review of historical pharmaceutical recalls and comparative issues with recent COVID-19 vaccines. Parallels with past drug withdrawals and gene-based vaccines include distortion of clinical trial data, with critical adverse event data absent from high-impact journal publications. Delayed regulatory action on pharmacovigilance data to trigger market withdrawal occurred with Vioxx (rofecoxib) and is apparent with the gene-based COVID-19 vaccines. Public health requires access to raw clinical trial data, improved transparency from corporations and heightened, active pharmacovigilance worldwide."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

Chemopreventive strategies for sporadic colorectal cancer: a narrative review. (PubMed, Transl Gastroenterol Hepatol) - "NSAIDs have proven promising in sporadic CRC chemoprevention but have been limited due to increased cardiovascular risk, particularly for celecoxib and rofecoxib. There is active investigation into establishing the first sporadic CRC chemoprevention strategy. Building from previous trials, the choice of study population, selection of endpoints, safety and tolerability, availability of surrogate biomarkers, and novel mechanisms of action targeting the adenoma-carcinoma sequence remain important points to consider for all future trials of sporadic CRC chemoprevention."

Journal • Review • Cardiovascular • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor

Sequential Epidemiological Analyses of Real-World Data: A Tool for Prospective Drug Safety Surveillance from the Rofecoxib Example. (PubMed, Drug Saf) - "Our prospective drug safety monitoring setup showed that the risk of MI could have been detected 3.5 years before the ultimate market withdrawal of rofecoxib. However, further research is needed to validate this approach."

Journal • Real-world evidence • Cardiovascular • Ischemic stroke • Myocardial Infarction

The COX-2 Inhibitor Celecoxib Sensitizes Nasopharyngeal Carcinoma Cells to Ferroptosis. (PubMed, Curr Cancer Drug Targets) - "The COX-2 inhibitor celecoxib effectively sensitized nasopharyngeal cancer cells to ferroptosis induction."

Journal • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • CHAC1 • GPX4

Understanding network meta-analysis. (PubMed, World J Clin Cases) - "Recently, in the World Journal of Clinical Cases, studied the different non-steroidal anti-inflammatory drugs (meloxicam, celecoxib, naproxen, and rofecoxib) for juvenile idiopathic arthritis with network meta-analysis (NMA). NMA necessitates steps akin to those of conventional meta-analysis, involving a thorough literature search, assessment of potential trial biases, statistical analysis of reported pairwise comparisons for all relevant outcomes, and evaluation of overall certainty of evidence on an outcome-specific basis. However, NMA demands substantial resources, given its propensity to address broader inquiries, typically involving a larger number of studies at each phase of the systematic review, from screening to analysis, compared to traditional meta-analyses."

Journal • Retrospective data • Idiopathic Arthritis • Immunology • Rheumatology

Anticancer and Cyclooxygenase Inhibitory Activity of Benzylidene Derivatives of Fenobam and its Thio Analogues. (PubMed, Curr Med Chem) - "Moreover, in silico ADMET predictions showed adequate properties for these compounds, making them promising leads worthy of further optimization."

Journal • Breast Cancer • Cervical Cancer • Oncology • Ovarian Cancer • Solid Tumor