Disalcid (salsalate) / Bausch Health - LARVOL DELTA

Jiangtang Decoction for Type 2 Diabetes and NAFLD: Integrative Analysis via Network Pharmacology, Mendelian Randomization, Molecular Docking, and In Vitro Validation. (PubMed, Endocr Metab Immune Disord Drug Targets) - "This study identified eight genes that are genetically predicted to be causal for the therapeutic effects of JTD on both T2DM and NAFLD, thereby establishing a genetic link between the conditions. These targets and associated pathways illuminate common underlying mechanisms, supporting JTD's potential for integrated treatment strategies and providing a basis for further investigation."

Journal • Preclinical • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • ALDH2 • CDH1 • EP300 • IL1B • PRKAB1 • TCF4

Omega-3 Fatty Acid Lipidomics in Diabetes Peripheral Neuropathy (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: University of Iowa | Trial completion date: Jan 2026 ➔ Jul 2027 | Trial primary completion date: Jul 2025 ➔ Feb 2027

Trial completion date • Trial primary completion date • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • Type 2 Diabetes Mellitus

Phytotherapeutic insights into hyperuricemia: a mechanistic and clinical perspective. (PubMed, Inflammopharmacology) - "Classical natural agents like salicylic acid and salsalate have also been reappraised for their mild uricosuric activity and anti-inflammatory action, offering a pharmacological bridge between traditional herbals and modern therapeutics...The article further explores the future scope of herbal treatments, emphasizing the need for large-scale clinical trials, regulatory approvals, and the development of standardized formulations to ensure consistency and efficacy. By integrating herbal interventions with conventional therapies, there is potential for improving patient outcomes for the management of HU, with few side effects."

Journal • Review • Gout • Inflammation • Inflammatory Arthritis • Nephrology • Renal Calculi • Rheumatology

Angiotensin II and Chronic Inflammation in Persistent Microvascular Dysfunction Following Preeclampsia (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: University of Iowa | Recruiting ➔ Completed

Trial completion • Gynecology • Inflammation

In silico study of salicylic acid derivatives as inhibitors of Ebola proteins through molecular docking. (PubMed, Comput Biol Chem) - "This study evaluates the inhibitory potential of six salicylic acid derivatives including aspirin, diflunisal, fendosal, fosfosal, salicylic acid, and salsalate; against three key Ebola virus receptor proteins through in-silico analysis. Among the derivatives screened, those targeting the VP35 protein exhibited superior binding energy, glide energy, glide Emodel, glide Evdw, and glide ligand efficiency, alongside the lowest RMSD values. These findings suggest that salicylic acid derivatives hold promise as potential anti-Ebola therapies and warrant further investigation in clinical trials."

Journal • Ebola Virus Disease • Hematological Disorders • Infectious Disease

Salsalate improves the anti-tumor efficacy of lenvatinib in MASH-driven hepatocellular carcinoma. (PubMed, JHEP Rep) - "Combined LEN and SAL improved survival and MASH-HCC pathology in mouse models without adverse effects. Given that SAL is a safe, economical, and approved medication, this concept holds great translational potential that could provide a new treatment avenue for patients with unresected MASH-HCC."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Inflammatory Arthritis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Rheumatoid Arthritis • Rheumatology • Solid Tumor • ATF3 • ETS1 • HIF1A

SAL-AD: Salsalate in Patients Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Adam Boxer | Active, not recruiting ➔ Completed | Phase classification: P1b ➔ P1

Phase classification • Trial completion • Alzheimer's Disease • CNS Disorders

Salsalate Negatively Impacts Microvascular Function in Women with Endometriosis. (PubMed, Am J Physiol Heart Circ Physiol) - "Increasing doses of acetylcholine (ACh; dissolved in lactated Ringer's) were perfused, alone (control) or co-perfused with: NG-nitro-L-arginine methyl ester (L-NAME), atorvastatin (statin), or L-NAME + statin (combo). Maximal vasodilation was then induced (local heat 43ºC + sodium nitroprusside perfusion)...FMD was not different between treatments (p=0.79). Salsalate treatment impairs vasodilation in the cutaneous microcirculation in women with endometriosis through non-NO-dependent mechanisms."

Journal • Cardiovascular • Endometriosis • Gynecology • Inflammation • Women's Health

The Role of Serum Free Fatty Acids in Endothelium-Dependent Microvascular Function. (PubMed, Endocrinol Diabetes Metab) - P2/3 | "Short-term reduction of FFA concentration does not improve insulin-stimulated vasodilation in patients with metabolic syndrome."

Clinical • Journal • Inflammation • Metabolic Disorders

Inflammatory Markers and Measures of Cardiovascular Autonomic Neuropathy in Type 1 Diabetes. (PubMed, J Am Heart Assoc) - P2/3, P3 | "Amongst several inflammatory biomarkers, suPAR, an immune-mediated glycoprotein, has a singular association with CAN measures. The potential of targeting suPAR as a disease-modifying approach for CAN in T1D warrants further exploration."

Journal • Cardiovascular • Diabetes • Diabetic Neuropathy • Inflammation • Metabolic Disorders • Pain • Type 1 Diabetes Mellitus

Role of Inflammation in Vascular Phenotype Associated with E-cigarette Use (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: University of Iowa | Not yet recruiting ➔ Recruiting

Enrollment open • Inflammation

Computational insights into human UCP1 activators through molecular docking, MM-GBSA, and molecular dynamics simulation studies. (PubMed, Comput Biol Chem) - "In this study, molecular docking of UCP1 activators, using 2,4-dinitrophenol (DNP) as a reference ligand (PDB ID: 8J1N, docking score: -5.343 kcal/mol), identified seven top-scoring compounds: naringin (-7.284 kcal/mol), quercetin (-6.661 kcal/mol), salsalate (-6.017 kcal/mol), rhein (-5.798 kcal/mol), mirabegron (-5.535 kcal/mol), curcumin (-5.479 kcal/mol), and formoterol (-5.451 kcal/mol). Additionally, most activators showed favorable intestinal absorption (>90 %) and lipophilicity (LogP 2-4), with pKa values supporting their pharmacological potential as UCP1-targeting therapeutics for obesity. These findings provide a foundation for designing potent UCP1 activators by integrating docking scores, interaction profiles, statistical profiles from MD simulations, and physicochemical assessments to develop effective anti-obesity therapies."

Journal • Genetic Disorders • Obesity

Role of Inflammation in Vascular Phenotype Associated With E-cigarette Use (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: University of Iowa

New P1 trial • Inflammation

TIN-PCOS-AOD: Treating Inflammation in Polycystic Ovary Syndrome to Ameliorate Ovarian Dysfunction (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: University of Illinois at Chicago | Recruiting ➔ Completed | N=90 ➔ 60 | Trial completion date: Jul 2024 ➔ Feb 2024 | Trial primary completion date: Jul 2024 ➔ Feb 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Inflammation • Obesity • Polycystic Ovary Syndrome

Inhibition of Nuclear Factor-KappaB Activation Improves Non-Nitric Oxide-Mediated Cutaneous Microvascular Function in Reproductive-Aged Healthy Women. (PubMed, Am J Physiol Heart Circ Physiol) - "Laser-doppler flux was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated as flux divided by mean arterial pressure and normalized to site-specific maximum (CVC%max; 28 mM sodium nitroprusside + 43 °C). Across treatments, there was a significant difference between the control and L-NAME sites, where both sites shifted upwards following salsalate treatment (both p<0.0001) while the L-NAME sensitive component was not different (p=0.94). These data demonstrate that inhibition of the transcriptional regulator NF-κB improves cutaneous microvascular function in reproductive-aged healthy women through non-NO-dependent mechanisms."

Journal • Cardiovascular • Inflammation

Investigation of Basolateral Targeting Micelles for Drug Delivery Applications in Polycystic Kidney Disease. (PubMed, Biomacromolecules) - "To address this, we identified four drug candidates from ADPKD clinical trials, bardoxolone methyl (Bar), octreotide (Oct), salsalate (Sal), and pravastatin (Pra), and incorporated them into peptide amphiphile micelles containing the RGD peptide (GRGDSP), which binds to the basolateral surface of renal tubules via integrin receptors on the extracellular matrix. Specifically, both Bar+Oct and Bar+Sal in the RGD micelle treatment showed enhanced therapeutic efficacy in ADPKD mice (Pkd1fl/fl;Pax8-rtTA;Tet-O-Cre) with a significantly lower KW/BW ratio and cyst index as compared to PBS and free drug-treated controls, while other combinations did not show a significant difference. Hence, we demonstrate that renal targeting through basolateral targeting micelles enhances the therapeutic potential of combination therapy in genetic kidney disease."

Journal • Autosomal Dominant Polycystic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • PAX8

Salsalate: a pleotropic anti-inflammatory drug in the treatment of diabetes, obesity, and metabolic diseases. (PubMed, Inflammopharmacology) - "Anti-inflammatory agents are being tested as anti-diabetic agents such as the IL-1b antagonist, Anakinra, the IL-1b inhibitor, Canakinuma, the IL-6 antagonists such as Tocilizumab, Rapamycin (Everolimus), and the IKK-beta kinase inhibitor, Salsalate. Long-term safety and efficacy of Salsalate in the treatment of T2DM have been evaluated, which showed improved fasting plasma glucose and reduced HbA1C levels as well as reduced pro-inflammatory markers in T2DM patients. Current publication summarizes the literature review of pathophysiology of role of inflammation in T2DM and clinical efficacy and safety of Salsalate in the treatment of T2DM."

Journal • Review • Diabetes • Genetic Disorders • Immunology • Metabolic Disorders • Obesity • Oncology • Ophthalmology • Rheumatology • Type 2 Diabetes Mellitus • CRP • IL1B • IL6 • TNFA

Salsalate Improves Postprandial Glycemic and Some Lipid Responses in Persons With Tetraplegia: A Randomized Clinical Pilot Trial With Crossover Design. (PubMed, Top Spinal Cord Inj Rehabil) - "Positive effects were also seen for some lipid but not for inflammatory response markers. Given the relatively "healthy" metabolic profiles of the participants, it is possible that salsalate's effects may be greater and more consistent in people with less favorable metabolic milieus."

Clinical • Journal • Dyslipidemia • Inflammation

Interventions to Attenuate Cardiovascular Calcification Progression: A Systematic Review of Randomized Clinical Trials. (PubMed, J Am Heart Assoc) - "Currently, there are insufficient or conflicting data for interventions evaluated in clinical trials for mitigation of cardiovascular calcification. Therapy involving aged garlic extract appears most promising, but evaluable studies were small and of short duration."

Clinical • Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease

Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease. (PubMed, iScience) - "RNA sequencing revealed that short salsalate treatment, next to restoring energy metabolism toward wildtype levels, also affects cell proliferation and inflammation, in PKD. We show that salsalate positively affects major dysregulated processes in ADPKD: energy metabolism, cell proliferation, and inflammation, providing more insights into its working mechanisms."

Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Inflammation • Metabolic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • PKD1 • PRKD1

Environmental Toxins and Alzheimer's Disease: a Comprehensive Analysis of Pathogenic Mechanisms and Therapeutic Modulation. (PubMed, Mol Neurobiol) - "Drugs like epigallocatechin-gallate, neflamapimod, salsalate, dexmedetomidine, and atabecestat are in different phases of clinical trials targeting the pathways for possible treatment of AD. This review aims to culminate the correlation between environmental toxicants and AD development. We emphasized upon the signaling pathways involved in the progression of the disease and the therapeutics under clinical trial targeting the altered pathways for possible treatment of AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Metabolic Disorders • BACE1 • PARP1 • TNFA

Salsalate Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome (AHA 2023) - P2/3 | "Salsalate improved neither insulin sensitivity nor systemic inflammation, and it blunted insulin-stimulated vasodilation in patients with metabolic syndrome. Salsalate does not modulate systemic inflammation and worsens arteriolar endothelial dysfunction in patients with metabolic syndrome."

Clinical • Inflammation • Metabolic Disorders • CRP

Salsalate and/or metformin therapy confer beneficial metabolic effects in olanzapine treated female mice. (PubMed, Biomed Pharmacother) - "Conversely, metformin treatment, either alone or in combination with salsalate, improved indices of glucose metabolism and increased energy expenditure in olanzapine treated mice. Collectively, our findings provide evidence that dual therapy with both metformin and salsalate could be an efficacious approach with which to dampen the metabolic consequences of antipsychotic medications."

Journal • Preclinical • CNS Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Psychiatry • Schizophrenia

TINSAL-T1DN: Targeting Inflammation With Salsalate in Type 1 Diabetes Neuropathy (clinicaltrials.gov) - P2/3 | N=61 | Completed | Sponsor: University of Michigan | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ May 2023 | Trial primary completion date: Jun 2024 ➔ May 2023

Trial completion • Trial completion date • Trial primary completion date • Diabetes • Diabetic Neuropathy • Inflammation • Metabolic Disorders • Pain • Type 1 Diabetes Mellitus

Omega-3 Fatty Acid Lipidomics in Diabetes Peripheral Neuropathy (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: University of Iowa | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • Type 2 Diabetes Mellitus • IL10 • IL6 • TNFA