sulindac / Generic mfg. - LARVOL DELTA

A Validated LC-MS/MS Method for the Determination of Sulindac and Its Metabolite Su-EP‑C in Human Plasma and Their Pharmacokinetic Application in Healthy Volunteers. (PubMed, ACS Omega) - "The plasma matrix, at both -20 °C and -70 °C, remained stable for 52 days with 5 freeze-thaw cycles. The method was successfully applied to fasting and postprandial pharmacokinetic clinical trials of orally administered sulindac tablets."

Journal • PK/PD data

Sulindac as a precision microRNA modulator in early-stage K-Ras-driven oncogenesis. (PubMed, Cell Death Discov) - No abstract available

Journal • Oncology • KRAS

Pharmacological reversal of LPS-induced cognitive impairments: evidence for inflammation-dependent and independent mechanisms (Neuroscience 2025) - "Fifteen compounds proved effective in reversing cognitive deficits and were categorized as follows: i) Anti-inflammatory NSAIDs & Steroids: Ibuprofen, indomethacin, sulindac, dexamethasone...iii) Synaptic & Neurotransmitter Modulators: Memantine, donepezil, GRN 529. iv) Metabolic & Signaling Agents: Metformin, semaglutide, neflamapimod. Two interventions—nilotinib and methylene blue—were ineffective...The convergence of benefits across anti-inflammation, oxidative stress reduction, synaptic modulation, and metabolic regulation underscores the multifactorial nature of inflammation-driven neurodegeneration. Identifying both effective and ineffective agents highlights the model's translational potential and discriminative validity."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

Sulindac sulfide suppresses oncogenic transformation through let-7b-mediated repression of K-Ras signaling. (PubMed, Cell Death Discov) - No abstract available

Journal • Oncology • KRAS • MIRLET7B

Unexpected effects of antibiotics on microbiota-mediated drug metabolism in a fistulated dog model. (PubMed, Eur J Pharm Sci) - "We investigated the metabolism of metronidazole and sulindac, two structurally and pharmacologically distinct drugs, before and after broad-spectrum antibiotic treatment...These findings underscore the complexity of microbiota-host-drug interactions and provide important insights for the development of translational microbiome-pharmacology models. Additionally, the drawbacks over the use of antibiotic-treated animal models to study microbiota-drug interactions are discussed due to antibiotic-induced changes in intestinal permeability and efflux that may influence drug absorption and metabolism."

Journal

Preclinical Evaluation of the Efficacy of α-Difluoromethylornithine and Sulindac Against SARS-CoV-2 Infection. (PubMed, Viruses) - "Overall, our studies demonstrated that DFMO and Sulindac administration as the prophylaxis regimen provided strong protection against the lethal outcome of SARS-CoV-2 infection and that male mice benefited more from the polyamine-targeted antiviral treatment than female mice. Our findings underscore the importance of evaluation of the antiviral activity of the drugs in the context of sex and age."

Journal • Preclinical • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

The nonsteroidal anti-inflammatory drug sulindac reverses obesity-driven immunosuppression and triple-negative breast cancer progression. (PubMed, Breast Cancer Res) - No abstract available

Journal • Breast Cancer • Genetic Disorders • Obesity • Oncology • Solid Tumor • Triple Negative Breast Cancer

Sulindac for the Prevention of Mesothelioma in Mice (IMIG 2025) - "These data indicate that sulindac significantly decreases the incidence of asbestos-induced mesotheliomas in germline Bap1 heterozygous mice and prolongs the survival of adeno-Cre virus-injected Bap1f/f; Nf2ff; Cdkn2af/f mice. These findings provide rationale for possible chemoprevention trials with sulindac or other related NSAIDs in BAP1-mutation carriers and asbestos-exposed individuals."

Preclinical • Fatigue • Mesothelioma • Solid Tumor • BAP1

Functional impact of new repressors of radioiodide uptake (ATA 2025) - "Of the tested drugs, 3 significantly inhibited NIS function in TPC-1-NIS cells: Enalapril, amitriptyline and sulindac (66%, 50% and 58% suppression; p = 0.0021, 0.0005 and 0.0087, respectively)...Our preliminary work identifies and validates 3 commonly prescribed drugs which inhibit radioiodide uptake, with clear potential impact on patient outcomes."

Solid Tumor • Thyroid Gland Carcinoma

Functional impact of new repressors of radioiodide uptake (ATA 2025) - "Of the tested drugs, 3 significantly inhibited NIS function in TPC-1-NIS cells: Enalapril, amitriptyline and sulindac (66%, 50% and 58% suppression; p = 0.0021, 0.0005 and 0.0087, respectively)...Our preliminary work identifies and validates 3 commonly prescribed drugs which inhibit radioiodide uptake, with clear potential impact on patient outcomes."

Solid Tumor • Thyroid Gland Carcinoma

Next-generation precision medicine for pain. (PubMed, Mol Psychiatry) - "Top therapeutic matches overall were the medications lithium and ketamine, as well as the nutraceuticals omega-3 fatty acids and magnesium. Drug repurposing bioinformatic analyses also identified the potential of carvedilol, sirolimus, budesonide, berbamine, and quetiapine, as well as of medications already used to treat pain such as amyleine, sulindac, sufentanil, carbamazepine, and meclofenamic acid, that serve as de facto positive controls. Additionally, we show how personalized patient reports for doctors would look like based on blood biomarkers testing, to aid with objective assessment of severity and risk, as well with individualized matching to medications and nutraceuticals. Given the fact that pain disorders are highly prevalent, can severely affect quality of life, and even lifespan, there is an urgent need for insights and tools such as the ones we have developed to be applied to and improve clinical diagnosis, treatment, and prevention options."

Journal • Inflammation • Pain • Psychiatry • ANXA1 • CD55

Prescription Trends by Orthopedic Surgery Provider: Review of the Medicare Part D Prescribers - by Provider and Drug, 2013-2021. (PubMed, Orthopedics) - "In line with national guidelines, claims for NSAIDs are increasing and claims for opioid pain medications and AOMs are decreasing. Claims for outpatient antibiotics are increasing, which is of significant concern, given renewed focus on antibiotic stewardship."

Journal • Medicare • Reimbursement • Review • US reimbursement • Orthopedics • Pain

Synthesis, In-Silico Evaluation, ADME Analysis, and Molecular Dynamics Simulation of Novel β-Lactam Derivatives Based on Diclofenac and Sulindac With Anticancer and Antioxidant Activities. (PubMed, Chem Biodivers) - "ADMET predictions revealed favorable pharmacokinetic properties for all compounds, with compounds 16 and 17 exhibiting good membrane permeability, minimal toxicity aside from immunotoxicity, and adequate bioavailability. In addition, molecular dynamics simulations confirmed the structural stability and sustained binding of the 16-TTK and 17-TTK complexes under physiological conditions."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor

Sulindac modulates the response of triple negative breast cancer to anti-PD-L1 immunotherapy. (PubMed, bioRxiv) - "Despite the FDA's approval of therapies like Atezolizumab (anti- PD-L1) and Pembrolizumab (anti-PD-1) for certain TNBC cases, more than half of all TNBC patients, especially those with low PD-L1 levels and in advanced stages, remain unresponsive. Therefore, in combination therapy, sulindac downregulating exosomal PD-L1 leads to increased availability of PD-L1 Ab, which potentially improves the overall efficacy of anti-PD-L1 therapy. In conclusion, our findings provide unique insights into the mechanism of action and efficacy for sulindac as an immunomodulatory agent in combination with anti-PD-L1 therapy for the treatment of TNBC."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • GZMB • MIR570

Drug Repurposing Patent Applications October-December 2024. (PubMed, Assay Drug Dev Technol) - "Significantly, the contribution from Iceland is how to induce therapeutic hypothermia-but with entacapone, used in Parkinson's disease. The UK company, HealX, presents data showing that Angelman syndrome, an intractable neurodevelopmental disorder, could be treated with the common NSAID sulindac. Gliclazide, an old antidiabetic, could potentially treat schizophrenia, as inventors from Chinese Ping An-Shionogi report. These are only a few highlights from the stream of documents that have been issued towards the end of 2024."

Journal • CNS Disorders • Depression • Developmental Disorders • Movement Disorders • Ophthalmology • Pain • Parkinson's Disease • Psychiatry • Rare Diseases • Schizophrenia

Sulindac Sulfide Suppresses Oncogenic Transformation Through let-7b-Mediated Repression of K-Ras Signaling. (PubMed, bioRxiv) - "In human colon cancer tissues and cell lines, let-7b is downregulated, but restored upon SS treatment. These findings identify a novel let-7b/K-Ras/LIN28B/ERK regulatory axis targeted by SS and provide mechanistic insight into its role in early-stage cancer chemoprevention."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • KRAS • LIN28B • MIRLET7B

The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial) (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Duke University | Trial primary completion date: Apr 2026 ➔ Jul 2026

Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor • GNAS

Sulindac and Breast Density in Women at Risk of Developing Breast Cancer (clinicaltrials.gov) - P2 | N=62 | Completed | Sponsor: Alison Stopeck | Active, not recruiting ➔ Completed | N=150 ➔ 62

Enrollment change • Trial completion • Breast Cancer • Oncology • Solid Tumor

Phenyl boronic acid conjugated lipid nanoparticles for targeted delivery of gamma-secretase inhibitor to breast cancer cells. (PubMed, Drug Dev Ind Pharm) - "The major objective of the present study is to develop and evaluate phenyl boronic acid (PBA) conjugated solid lipid nanoparticles (PBA-SUL@SLN) for the targeted delivery of sulindac (SUL) to breast cancer (BC) cells.Significance: Utilizing a dual approach that combines PBA-mediated targeting with Notch-1 pathway inhibition by SUL, the study aims to enhance therapeutic selectivity and efficacy against an aggressive BC subtype, triple negative breast cancer (TNBC), which lacks well defined molecular targets...Cytotoxicity assays revealed strong and selective efficacy against TNBC cells while causing minimal effects on normal cells. The PBA-SUL@SLN formulation presents a promising targeted therapeutic strategy for TNBC, addressing key limitations of existing treatments."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • NOTCH1

Sulindac exhibits anti-proliferative and anti-invasive effects and enhances the sensitivity to paclitaxel in ovarian cancer. (PubMed, Front Pharmacol) - "Inhibition of cellular stress by N-acetylcysteine partially reversed the anti-proliferative and anti-invasive effects of sulindac. Treatment with sulindac for 4 weeks effectively reduced tumor growth, improved serum levels of inflammatory cytokines and chemokines, and reduced the expression of Cox-2 of ovarian tumors in KpB mice compared with untreated mice. These findings provide support for the development of clinical trials repurposing sulindac in the treatment of OC, possibly in combination with paclitaxel."

Journal • Oncology • Ovarian Cancer • Solid Tumor • PTGS2

A 40Year Journey: Adenocarcinoma in a J Pouch PostProphylactic Surgery for FAP (ASCRS 2025) - "Despite being on sulindac and mesalamine, pouch polyps persisted...Managing recurrent disease and complex surgery in elderly patients with comorbidities presents unique challenges. Further research is needed on risk factors for pouch malignancy and the role of chemoprevention."

Surgery • Cardiovascular • Colorectal Cancer • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity • Obstructive Sleep Apnea • Oncology • Respiratory Diseases • Sleep Disorder • Solid Tumor • Type 2 Diabetes Mellitus

Sulindac and Breast Density in Women at Risk of Developing Breast Cancer (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Alison Stopeck | Trial completion date: Feb 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

Clinical Challenges and Evolving Treatments in Desmoid Fibromatosis: A Single Institution Experience. (PubMed, Cancer Invest) - "In total, ten patients received medical therapy including tamoxifen/sulindac (n = 7), nirogacestat (n = 1), and sorafenib (n = 2). We also noted effective tumor control in patients receiving medical therapy. As such, surgery can be utilized in situations with well-demarcated DT which can be removed en bloc, while utilizing medical therapy for highly invasive tumors."

Journal • Desmoid Tumors • Fibrosis • Oncology • Sarcoma • Solid Tumor

A Common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice. (PubMed, Gut) - "This mouse strain provides evidence that the exon 6 deletion causes ER stress and inflammation and is an excellent model to understand its contribution to pancreatic cancer and identify preventive strategies."

Journal • Preclinical • Hepatology • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • AGR2

Crystal structure of the possible sulindac impurity 2-(5-fluoro-2-methyl-1H-inden-3-yl)aceto-nitrile. (PubMed, Acta Crystallogr E Crystallogr Commun) - "Single-crystal X-ray analysis revealed two conformationally slightly different mol-ecules in the asymmetric unit (Z' = 2), each containing an indene ring system. In the crystal structure, [100] chains formed through C-H⋯N inter-actions are connected into a tri-periodic supra-molecular structure by further C-H⋯F and C-H⋯π inter-actions through P21/n symmetry operations."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CDKN1A