indomethacin / Generic mfg. - LARVOL DELTA

Application of acoustic ejection mass spectrometry for plasma protein binding assay using flux dialysis. (PubMed, Drug Metab Dispos) - "Herein, we validated this approach using 10 commercially available compounds with known fu values-imipramine, indomethacin, itraconazole, lapatinib, nicardipine, warfarin, chlorpromazine, rivastigmine, zonisamide, and ritonavir-with a wide fu range covering from very high binding (fu ≤ 0.01) to low binding (fu > 0.10) in human plasma. SIGNIFICANCE STATEMENT: This study bridges the gap between flux dialysis and acoustic ejection mass spectrometry by creating a synergistic analytical framework for plasma protein binding assays, addressing limitations of both methods and enabling high-throughput applications with improved accuracy and efficiency. The combination of flux dialysis and acoustic ejection mass spectrometry will make a positive contribution to the development of high-throughput in vitro absorption, distribution, metabolism and excretion assays in drug discovery."

Journal

Study on the potential of limosilactobacillus fermentum laf - 09 of gastric origin in humans to prevent nsaids - induced gastric ulcers and acute gastric hemorrhage (ASH 2025) - "Methods : Twenty 6-8-week-old male C57BL/6 mice were randomly divided into 4 groups (Control group, Indomethacin group, LAF-09 group, ATCC group)... Limosilactobacillus Fermentum LAF - 09 of human gastric origin can effectively prevent NSAIDs - induced gastric ulcer and acute gastric hemorrhage by enhancing the antioxidant defense ability of gastric mucosa, protecting the integrity of tight junction barrier and positively regulating the gastric flora. (Acknowledgements:This study was supported by National Natural Science Foundation of China. Grant No32370139 to Hongying Fan)"

Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Inflammation • Peptic Ulcer • IL1B • IL6 • OCLN • PTGS2 • TJP1 • TNFA

Phosphatidylserine-rich platelet blebs enhance hemostasis after mucous membrane injury but not after skin or vascular injury: Studies with ANO6-deficient mice (ASH 2025) - "Gastric ulcers were induced by indomethacin via gastric gavage.Gastric bleeding was evaluated over the next 64 hr using a chemiluminescence assay for heme in mousefeces...Our data suggest that formation of PS-rich plateletblebs and the quantity of PS on the blebs is not rate-limiting for ordinary hemostasis. These data suggestthe presence of an uncharacterized mechanism of coagulation suppression on PS-rich plateletmembranes when the level of coagulation initiation is low or moderate."

Preclinical • Peptic Ulcer • ANO6 • ANXA5

Heightened anti-inflammatory and antioxidant effects of bone marrow stem cell-conditioned media with mono and doped TiO2 nanoparticles in Carrageenan-induced inflammation. (PubMed, Inflammopharmacology) - "A pre-study screening using three doses (10, 20, and 50 mg/kg) demonstrated a dose-dependent reduction in paw edema, with the 50 mg/kg dose showing the highest inhibition, comparable to indomethacin...Histopathological assessment confirmed these findings, showing nearly normal dermal architecture with minimal inflammatory infiltration. The results highlight the synergistic therapeutic potential of doped TiO₂ nanoparticles and BM-MSC-CM in mitigating inflammation and oxidative stress."

Journal • Inflammation • CD34 • CD73 • IL10 • IL4 • IL6 • PTPRC • THY1 • TNFA

Computational and bioactivity investigations of flavonoid fraction from Dodonaea viscosa against oxidative stress and inflammation. (PubMed, Sci Rep) - "It also exhibited strong dual inhibitory effects against COX-2 (IC₅₀ = 38.21 μg/mL) and 5-LOX (IC₅₀ = 40.72 μg/mL), comparable to indomethacin (IC₅₀ = 33.03 μg/mL) and zileuton (IC₅₀ = 33.41 μg/mL). Molecular docking further validated the strong binding affinities of the major flavonoids, with isokaempferide showing particularly stable interactions with COX-2, 5-LOX, and NAD(P)H oxidase. MM-GBSA and hydrogen bond analyses highlighted key residues involved in target inhibition, reinforcing the experimental findings and supporting the potential of D. viscosa flavonoids as promising multifunctional therapeutic leads."

Journal • Inflammation

Syringic acid protects against indomethacin-induced gastric injury via NF-κB and apoptotic pathway modulation. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Syringic acid may confer gastroprotective effects against indomethacin-induced gastric injury by modulating oxidative stress, inflammation, and apoptosis. While less potent than omeprazole, its multi-target actions suggest potential value as an adjunctive strategy for COX inhibitor-induced gastric damage."

IO biomarker • Journal • Inflammation • Peptic Ulcer • BAX • BCL2 • CASP3

Mechanistic Insights into Semi-Solid Extrusion 3D Printing of Indomethacin-Nicotinamide Cocrystal-Loaded Oral Fast-Dissolving Films. (PubMed, Eur J Pharm Sci) - "Dissolution profiles were consistent across cocrystal loadings and remained statistically equivalent for films printed from inks stored for up to 2 days, as well as for the 3-day redispersed ink, confirming that the structural reinforcement required for printability does not compromise rapid release performance. Overall, this work provides mechanistic insight into the formulation-process-performance relationships governing SSE 3D printing of cocrystal-loaded OFDFs and highlights the potential of this green, low-temperature platform for decentralized, patient-centric manufacturing of fast-dissolving dosage forms."

Journal

Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review. (PubMed, Cells) - "Most studies relied on classical adipogenic inducers, including isomethylbutylxanthine, dexamethasone, and insulin, with additional use of triiodothyronine, rosiglitazone, or indomethacin. A key limitation remains the predominant reliance on gene expression as the primary outcome, with few studies assessing mitochondrial respiration or broader metabolic functions. Moving forward, the development and adoption of standardized, functionally validated protocols will be critical to fully realize the potential of human in vitro thermogenic adipocyte models in metabolic research."

Journal • Review • Metabolic Disorders

Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial. (PubMed, JAMA) - P3 | "Infants with PDA were randomized to expectant management (n = 242) or active treatment (n = 240; acetaminophen, ibuprofen, or indomethacin) to close the PDA...Survival was substantially higher with expectant management. ClinicalTrials.gov Identifier: NCT03456336."

Clinical • Journal • Bronchopulmonary Dysplasia • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Ternary phase optimized indomethacin nanoemulsion hydrogel for sustained topical delivery and improved biological efficacy. (PubMed, Sci Rep) - "The fluorescence intensity measurements of IM-loaded nanoemulsion during cellular uptake remained steady at 742 at 2 h, then decreased to 698 at 4 h and 695 at 6 h, indicating stable internalization. However, NEG-IM demonstrated a slow rise in uptake over 6 h from 212 to 536 in fluorescence intensity results."

Journal • Inflammation

Post-endoscopic retrograde cholangiopancreatography pancreatitis: Mechanistic pathways, diagnostic benchmarks, and emerging and mitochondria-targeted therapies. (PubMed, World J Gastrointest Surg) - "Rectal non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, inhibit prostaglandin synthesis...This article reviews the epidemiological and pathophysiological foundations of PEP, evaluates evidence-based preventive strategies (e.g., NSAIDs, pancreatic duct stenting), and discusses emerging approaches such as gene therapy. It also summarizes advances in treating mild and severe PEP, highlights the role of MDT care, identifies current knowledge gaps, and proposes directions for future research, including the discovery of novel biomarkers and the development of personalized preventive and therapeutic strategies."

Journal • Review • Cardiovascular • Gene Therapies • Hypertension • Infectious Disease • Inflammation • Pancreatitis • NLRP3

Comparison of Rectal Indomethacin and Diclofenac for post ERCP Pancreatitis Prophylaxis: A Single Center Study. (PubMed, Clin Res Hepatol Gastroenterol) - "This study suggests that rectal diclofenac may offer a slight advantage over indomethacin in preventing PEP, particularly in high-risk groups, such as patients undergoing sphincterotomy; which was not previously published in the existing literature."

Journal • Pancreatitis

Pre-operative IRX-2 in Early Stage Breast Cancer (ESBC) (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Providence Health & Services | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Male Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

The "double-edged sword" effect of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of endometriosis (EMS). (PubMed, Reprod Biol Endocrinol) - "1Proposing a New Paradigm: By constructing a multi-dimensional analytical framework that integrates network toxicology, causal inference, and structural biology, this study is the first to reveal the"target-oriented heterogeneous effects" of NSAIDs in the treatment of dysmenorrhea caused by endometriosis, challenging the traditional "one-size-fits-all" treatment model.2 Identifying Key Targets: This study established a complete evidence chain from "target screening" to "causal inference" and finally to "structural validation," identifying for the first time EPHB4 as the central hub gene mediating the potential risk effects of NSAIDs and elucidating that its function is primarily achieved through angiogenesis pathways.3Elucidating a Complex Mechanism: Through cross-validation between genetic causality and molecular structural simulation, we elucidated the unique "dual regulation" mode of indomethacin:..."

Journal • Endometriosis • Gynecology • Pain • Women's Health • EPHB4 • PTGER4

Vasodilatory effects of trans-3-methoxy-β-nitrostyrene, a synthetic nitroderivative, on rat thoracic aorta: involvement of soluble guanylate cyclase stimulation. (PubMed, J Cardiovasc Pharmacol) - "T3MN-induced vasodilatory effects remained unaffected by indomethacin, MDL-12,330A or glybenclamide but were significantly reduced by endothelium removal, L-NAME, ODQ, LY294002, TEA, 4-AP, and apamin. Under Ca2+-free conditions, T3MN was unresponsive to transient contractions evoked by caffeine, whereas it inhibited contractions induced by (i) the protein kinase C activator phorbol 12-myristate 13-acetate, (ii) the tyrosine phosphatase inhibitor sodium orthovanadate, (iii) exogenous calcium influx via receptor- or voltage-operated Ca2+ channels and (iv), in an ODQ-preventable manner, those evoked by PHE or Ca2+ influx through stores-operated Ca2+ channels activated by thapsigargin-induced Ca2+ store depletion. In conclusion, T3MN induced a potent vasorelaxant effect that seems to be mediated partly by an endothelium-dependent mechanism involving activation of the Akt/eNOS/NO pathway and partly by an endothelium-independent mechanism through activation of the sGC/cGMP/PKG..."

Journal • Preclinical • NOS3

Benchmarking CuₙO (n = 1, 2) complexes via ab initio methods: structural, electronic, and thermodynamic insights with biochemical relevance. (PubMed, J Mol Model) - "In this context, we extend our analysis to the Cu(II)/indomethacin complex, illustrating how the lessons learned from the fundamental systems can be applied to biologically relevant copper-ligand interactions...In addition, electronic and structural properties of Cu₂ and CuO-such as ionization potentials, electron affinities, vibrational frequencies, equilibrium bond lengths, and spin or magnetic coupling constants-were calculated. Computational results were validated through comparison with available experimental data."

Journal • Tyrosinase

Robust Machine Learning-Driven Drug Repositioning Pipeline for Classical Subtype of Pancreatic Ductal Adenocarcinoma. (PubMed, Annu Int Conf IEEE Eng Med Biol Soc) - "Through our pipeline, we successfully identified at least five promising drug candidates for PDAC, including Indomethacin, Sorafenib, Valproic Acid, Cyclosporine, and Irinotecan, showcasing the potential of our drug repositioning methodology. There were at least five promising drug candidates predicted through our pipeline. Our findings may assist clinicians in considering the proposed drug candidates to enhance treatment strategies and improve patient outcomes in PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers (clinicaltrials.gov) - P1 | N=36 | Terminated | Sponsor: National Cancer Institute (NCI) | Completed ➔ Terminated; Site plans to become a site for a multicenter study of this therapy

IO biomarker • Trial termination • Gene Therapies • Lung Cancer • Oncology • Solid Tumor

The sesquiterpene lactone components of Cichorium glandulosum suppress both in vitro and in vivo inflammatory responses by reducing IL-1β levels. (PubMed, Inflammopharmacology) - "Animal studies further confirmed the anti-inflammatory effects of these compounds in an acute inflammation model, with Lactucopicrin demonstrating superior anti-inflammatory efficacy compared to the positive control, indomethacin. Structure-activity relationship studies identified the α-methylene-γ-lactone group in sesquiterpene lactones as the key pharmacophore responsible for their anti-inflammatory activity. In conclusion, sesquiterpene lactones in Cichorium glandulosum inhibit inflammation by targeting IL-1β, demonstrating significant anti-inflammatory potential and providing new theoretical insights into the pharmacological research of active components in Cichorium glandulosum."

Journal • Preclinical • Inflammation • IL1B • IL6 • TNFA

Network pharmacology reveals Ficus. Carica. L latex as a potential therapeutic agent for gastric ulcers by modulating inflammation and promoting repair. (PubMed, PLoS One) - "FCL significantly alleviated the indomethacin-induced ulceration and reduced the ulcer index...Additionally, an in-silico study using annotated FCL compounds highlighted Ficuseptin-C, Ficuseptin-B and Ficusin-A in the extract may contribute to its antiulcer properties. The present study highlighted the potential of FCL as a promising natural gastro-protective agent."

Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Inflammation • Peptic Ulcer • EGF • FGFR • IGF1 • IL1B • IL1R1 • IL6 • TGFB1 • TNFA

Case report: Retinal involvement in recurrent painful ophthalmoplegic neuropathy with reversible color vision impairment (EHF-EHC 2025) - "Acute treatments (rizatriptan, ibuprofen, loxoprofen, rimegepant) failed; only indomethacin provided relief. Interictal IV nitroglycerin failed to induce migraine-like headache...By inhibiting cyclooxygenase (COX), indomethacin suppresses prostaglandin synthesis, reducing prostaglandin-mediated sensitization of trigeminovascular afferents, suggesting trigeminovascular afferent sensitization in RPON. Furthermore, RPON pathophysiology may involve retinal neuronal networks beyond the oculomotor nerve, supported by PERG amplitude changes implicating inner retinal layer pathology, indicating pathogenesis distinct from classical cranial neuropathies."

Case report • Clinical • CNS Disorders • Migraine • Neuralgia • Ophthalmology • Pain

Challenging the criteria: A case of unclassifiable trigeminal autonomic-like headache (EHF-EHC 2025) - "Frovatriptan provided fast relief, although some residual pain persists for up to 1 day. Indomethacin was tried but rapidly dismissed due to side effects...Despite the atypical pain duration, the presence of prominent autonomic signs and the partial response to Verapamil favours a diagnosis within the trigeminal autonomic cephalalgia spectrum, highlighting the diagnostic complexity of these entities. Disclosure:the patient gave her informed consent to publish her details."

Clinical • Mood Disorders • Pain

Benign episodic unilateral mydriasis and headache: More than meets the eye (EHF-EHC 2025) - "Indomethacin and oral corticosteroids were not useful. Lamotrigine 100mg BD resulted in resolution of the pain, but with ongoing episodes of mydriasis...Contrast-enhanced MRI and MRA brain imaging showed incidental prominent optic nerve sheaths and intrasellar arachnoid herniation (without clinical signs of papilloedema) bilaterally, but no other relevant findings. These two cases highlight the likely association of headache with BEUM, suggesting possible shared biological pathways."

CNS Disorders • Migraine • Musculoskeletal Pain • Ophthalmology • Pain

The real pain of abuse: Not all bruises are visible (EHF-EHC 2025) - "The hypothesis of short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) was considered, but there was no response to either lamotrigine nor topiramate at therapeutic doses...The hypothesis of hemicrania continua was considered, but again there was no response to indomethacin...Nonetheless, it is of supreme importance to systematically inquire about prior or ongoing physical, emotional, and/or sexual abuse. Emphasis is on the complex diagnostic process, the critical role of a multidisciplinary approach, and the consideration of the patients' emotional and social dimensions."

Cardiovascular • CNS Disorders • Depression • Dermatology • Fibromyalgia • Hypertension • Mental Retardation • Mood Disorders • Musculoskeletal Pain • Ophthalmology • Pain • Rheumatology

Primary cough headache – Botulinum toxin protocol treatment with a new indication? (EHF-EHC 2025) - "Indomethacin is the first-line treatment, but alternatives like acetazolamide or cerebrospinal fluid drainage have shown benefit in refractory or contraindicated cases...Initial treatment with flunarizine was ineffective...Trials with amitriptyline and propranolol were unsuccessful. A PREEMPT protocol with botulinum toxin was initiated, resulting in a reduction in headache frequency to 15 days/month after the first cycle, and fewer than 5/month after the second, with sustained improvement. Botulinum toxin is a safe and effective therapeutic option for PCH, especially in patients unresponsive to or intolerant of standard pharmacological treatments."

Clinical • Cardiovascular • CNS Disorders • Cough • Gastroenterology • Hypertension • Migraine • Otorhinolaryngology • Pain • Rare Diseases • Renal Disease • Respiratory Diseases • Sleep Disorder • Vertigo