tolfenamic acid / Generic mfg. - LARVOL DELTA

Machine learning analysis of oral solid dosage formulation solubility variations by adjusting pressure and temperature. (PubMed, Sci Rep) - "This study helps pharmaceutical and chemical companies predict tolfenamic acid solubility and SC-CO2 density. The proposed models and ChOA hyper-parameter optimization solve solubility and density prediction problems in research and industry."

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In vitro dynamic and quantitative monitoring of strigolactone-signaling complex formation by time-resolved FRET. (PubMed, Plant J) - "In addition, we found that tolfenamic acid, an antagonist of the SL receptor, inhibited the SL-induced PPI but could not disrupt the already-formed signaling complex. The TR-FRET system was also used to rapidly and specifically detect naturally occurring SLs from root exudates containing many impurities. This work provides insights into the molecular mechanism of SL perception as well as a powerful tool for activity-based screening of SL signaling modulators."

Journal • Preclinical • Targeted Protein Degradation

Crystal Morphology and Associated Face-Specific Growth Kinetics of Tolfenamic Acid as a Function of Its Solution Crystallization Environment. (PubMed, Cryst Growth Des) - "This is in contrast to the capping faces, which is found to be less well-defined with mass transfer and surface integration being more balanced depending on the degree of solution supersaturation. The interplay between solvent-dependent surface interactions and intermolecular packing with the crystal face-specific growth kinetics is highlighted, contributing well toward the development of a predictive framework for the design and control of the solid-form properties of organic materials."

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Pluripotent Cinnamic Acid and Valproic Acid Hybrid Molecules Designed as Strong Anti-inflammatory and Anti-hyperlipidemic Compounds. (PubMed, Med Chem) - "The multiple activities of the synthesized compounds may serve for the manipulation of conditions involving inflammation and lipid deregulation, or the further optimization and production of compounds towards these ailments."

Journal • Cardiovascular • Dyslipidemia • Inflammation • Metabolic Disorders

COX-2 targeting Ru-arene complexes from metal-ligand synergistic enhancement strategy for breast cancer therapy. (PubMed, J Inorg Biochem) - "Toxic Ru-tol was synthesized from the non-toxic precursors aryl ruthenium azide and tolfenamic acid...Ru-tol demonstrated supeior penetration capacity and antiproliferative efficacy in 3D multicellular tumor spheroids (MCTS), suggesting the potent clinical applications. This work not only demonstrated the efficiency of MLSE strategy for the development of novel anti-cancer metal-based drugs, but also presented a promising target for the TNBC treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • MMP9 • PTGS2

Pharmacokinetics of Tolfenamic Acid Administered Orally and Intravenously at Different Doses in Pekin Ducks (Anas platyrhynchos domestica). (PubMed, Animals (Basel)) - "In ducks, tolfenamic acid's plasma protein binding was 99.74%, unaffected by concentration. These results may contribute to the application of tolfenamic acid in ducks at different doses, but dose-related changes in therapeutic efficacy should also be demonstrated."

Journal • PK/PD data

Pregnancy rate after treatment with a nonsteroidal anti-inflammatory drug (tolfenamic acid) at the time of embryo transfer in recipient cows. (PubMed, Theriogenology) - "Additionally, NSAID treatment improved pregnancy rates in recipients receiving in vitro-produced embryos at the morula stage (P = 0.05) but not at the early to expanded blastocyst stages (P = NS). In conclusion, we suggest that TA may provide reproductive benefits under specific ET situations, particularly in heifers and recipients with physiological or embryonic conditions commonly associated with reduced fertility."

Journal • Inflammation

Mechanistic investigation of methadone, tolfenamic acid, and cilnidipine in traumatic brain injury: a novel multi-target perspective outcome of network pharmacology. (PubMed, Inflammopharmacology) - "This study identified a primary target for MTD such as NOS1, NOS2, NOS3, DRD2, DAT (SLC6A3), MPO, SLC6A4, CXCR4-C-X-C, AKT1, SLC/8A2, HTR1A; for TA: MAPK1, GRIN1 and for CLD: IGF1R, DRD2, SHH, MAP2K1, CACNA1D, HTR2A, PDE4D, CASP3, MTOR, FASN, PTGS2, SCN9N, CNR1, CACNA1C, ABCB1, PIK3CA, GSK3B in the mechanistic regulation of TBI by reducing the activation of several pathways linked to development of TBI."

Journal • CNS Disorders • Vascular Neurology • ABCB1 • CASP3 • CXCR4 • DRD2 • FASN • HTR2A • MAP2K1 • MAPK1 • NOS1 • NOS2 • NOS3 • PACERR • PIK3CA • PTGS2 • SLC6A3 • SLC6A4

NSAIDS AS MODULATORS OF CATION CHANNELS: FENAMATES REPURPOSING IN CHANNELOPATHIES. (PubMed, ChemMedChem) - "In this review, we describe the ability of fenamates (i.e. niflumic, flufenamic, mefenamic, meclofenamic and tolfenamic acids) to differentially modulate the activity of cationic ion channels. Overall, preclinical and clinical studies suggest that fenamates represent a promising class of compounds for drug repurposing and for the development of new molecules, offering novel therapeutic opportunities for patients affected by ion channel-related disorders."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Oncology • Pain

Pleiotropic Effects of the NSAID Fenamates on Chloride Channels: Opportunity for Ion Channelopathies? (PubMed, Pharmacol Res Perspect) - P=N/A, P1/2 | "This narrative review resumes the effects of niflumic acid (NFA), flufenamic acid (FFA), mefenamic acid (MFA), meclofenamic acid (MCFA), and tolfenamic acid (TFA) on different types of chloride channel. Therefore, thanks to their variegated modulatory activity on chloride channels, fenamates might be considered promising lead compounds for the development of new drug candidates that can target these altered channels involved in channelopathies. Trial Registration: EudraCT number: 2021-000708-39; ClinicalTrials.gov identifier: NCT029930005 and NCT02429570."

Journal • Review • CNS Disorders • Cystic Fibrosis • Epilepsy • Genetic Disorders • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Ophthalmology • Otorhinolaryngology • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Characterization of feline nonsteroidal anti-inflammatory drug activated gene-1 (fNAG-1) and its protective function in kidney cells. (PubMed, BMC Vet Res) - "This study highlights the significant role of NAG-1 in feline kidney cells, revealing its high expression in the liver and kidney and demonstrating its protective effects on kidney function. These results underscore the potential of NAG-1 as a key factor in kidney protection. Future research should focus on further elucidating the molecular pathways involved and exploring therapeutic strategies to harness NAG-1 for managing obesity-related renal dysfunction in cats."

Journal • Genetic Disorders • Nephrology • Obesity • Renal Disease • BAX • GDF15

Non-covalent binding of non-steroidal anti-inflammatory drugs to antibiotics: preparation, characterization, physicochemical properties and study of single crystals of tolfenamic acid-enrofloxacin drug-drug salt and their antibacterial and anti-inflammatory activities. (PubMed, Int J Pharm) - "The in vitro antimicrobial activity and anti-inflammatory activity of TA-ENR were also somewhat improved compared to TA and ENR. The success of this work implies that we may provide new ideas for designing and synthesizing solid drugs with better physicochemical properties and bioactivity, as well as for the treatment of septic arthritis, through the formation of drug-drug co-crystals/salts."

Journal • Immunology • Rheumatology

Pharmacokinetic Characteristics of Tolfenamic Acid in Freshwater Crocodiles (Crocodylus siamensis). (PubMed, Animals (Basel)) - "Good bioavailability levels and favorable plasma concentrations of TA were obtained in freshwater crocodiles after IM administrations, considering that this is the preferred route of drug administration in freshwater crocodiles. Multi-dose and pharmacodynamic studies are needed to better establish the safety and efficacy of using TA in this crocodilian species."

Journal • PK/PD data

Local Antimicrobial Potential of Bupivacaine and Tolfenamic Acid-Loaded Ultra-High Molecular Weight Polyethylene (UHMWPE) for Orthopedic Infection. (PubMed, Bioengineering (Basel)) - "For the dual drug-loaded UHMWPE, the drug release rate from BP/TA combinations was interestingly not a direct function of the loaded drug weight percent, potentially due to the hydrophobicity of TA and the interactions between the two drugs. Combinations of BP and TA at the higher total drug concentration (10 and 20%) showed a prolonged antibacterial effect against S. aureus, with great potential for prophylactic use."

Journal • Infectious Disease • Orthopedics • Pain

Ru(II)-Fenamic-Based Complexes as Promising Human Ovarian Antitumor Agents: DNA Interaction, Cellular Uptake, and Three-Dimensional Spheroid Models. (PubMed, Inorg Chem) - "Cancer resistance to chemotherapeutic agents such as cisplatin presents a significant challenge, leading to treatment failure and poor outcomes...Four Ru(II) complexes with fenamic acid derivatives were synthesized and characterized: [Ru(L)(bipy)(dppp)]PF6, where L represents fenamic acid (HFen, complex 1), mefenamic acid (HMFen, complex 2), tolfenamic acid (HTFen, complex 3), and flufenamic acid (HFFen, complex 4)...These complexes also altered cell morphology, reduced cell density, and inhibited colony formation in the A2780 cells. Staining assays indicated induced cell death and organelle damage, highlighting their potential as promising antitumor agents."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Degradation of fenamates. (PubMed, Profiles Drug Subst Excip Relat Methodol) - "The clinically prescribed drugs of the fenamate group include mefenamic acid, tolfenamic acid, meclofenamic acid, flufenamic acid, and niflumic acid. Studies have been performed to remove these contaminants from water sources by various forced degradation procedures, but the number of studies in this area is limited. In this chapter, an effort has been made to review the degradation of multiple fenamates in different systems and the factors affecting the degradation rates with the proposed degradation pathways."

Journal • Review • Pain

Structural and theoretical studies of amantadinium fenamates. (PubMed, Acta Crystallogr B Struct Sci Cryst Eng Mater) - "Two new crystals of amantadinium salts were obtained from fenamic and tolfenamic acid. The salt of fenamic acid is a model compound for interaction analysis, while amantadinium tolfenamate is a composition of a drug used in the treatment of symptoms of Parkinsonism and as a nonsteroidal anti-inflammatory drug. The crystal structures were studied and a theoretical analysis of the hydrogen bonds and weak interactions was carried out using quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) methods."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Green synthesis, anti-inflammatory evaluation and molecular docking of novel pyridines via one pot multi-component reaction using ultrasonic irradiation. (PubMed, Mol Divers) - "The anti-inflammatory activity of the newly compounds was examined with the reference drug Ibuprofen. Furthermore, the newly compounds were studied in their molecular docking simulations against the enzyme Human Cyclooxygenase-2, with Tolfenamic Acid as a reference ligand (PDB ID: 5IKT). Compound 4b demonstrated a robust binding affinity with the target protein 5ikt, evidenced by its binding affinity score of - 11.16 kcal/mol, which is the highest among the studied compounds."

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Perioperative pain management in dogs and cats: Attitudes and practices among Thai veterinarians. (PubMed, Vet Anaesth Analg) - "This study reveals variations in perioperative pain management practices in dogs and cats among veterinarians, influenced by sex, graduation year, education and workplace."

Journal • Anesthesia • Pain

Repurposing Tolfenamic Acid to Anchor the Uncharacterized Pocket of the PUB Domain for Proteolysis of the Atypical E3 Ligase HOIP. (PubMed, ACS Chem Biol) - "Although tolfenamic acid did not block the substrate recognition and linear ubiquitination activity of HOIP, a ligand of the uncharacterized PUB pocket of HOIP (LUPH), by chemical linking pomalidomide with tolfenamic acid, degraded HOIP, reduced NEMO ubiquitination and p65 phosphorylation, and eventually inhibited NF-κB activation and breast cancer cell proliferation. Our work proposes an alternative strategy to target the nonfunctional pocket of the PUB domain with high sequence diversity to promote HOIP degradation, rather than targeting the conserved RBR domain to block the catalytic function of HOIP."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Synthesis, structure and biological activity of silver(I) complexes containing triphenylphosphine and non-steroidal anti-inflammatory drug ligands. (PubMed, J Inorg Biochem) - "The binding properties of tolfenamic acid, ibuprofen and the two complexes with DNA and BSA were investigated using UV or fluorescence spectroscopy. The intracellular reactive oxygen species (ROS) assay showed complex 1 induced the ROS generation in HeLa cells in a concentration dependent manner. Flow cytometry analysis showed complex 1 could suppress the HeLa cells growth during the G0/G1 phase and induce apoptosis in dose-depended manner."

Journal • Oncology

Pharmacokinetics of tolfenamic acid in ducks (Anas platyrhynchos domestica) after different administration routes. (PubMed, Br Poult Sci) - "Tolfenamic acid was absorbed rapidly, eliminated quickly and exhibited a small distribution volume in Pekin ducks. Pharmacokinetic parameters, including maximum concentration, area under the plasma concentration - time curve and bioavailability, were found to be different in ducks from other bird species."

Journal • PK/PD data • Pain

Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep. (PubMed, Vet Med Sci) - "A decrease in plasma elimination and an increase in plasma concentration of tolfenamic acid were observed depending on the dose. Tolfenamic acid lowly passed into sheep's milk at 2 and 4 mg/kg doses. This study may provide valuable information for clinicians' decision-making processes."

Journal • PK/PD data

Coordination compounds of cobalt(II) with carboxylate non-steroidal anti-inflammatory drugs: structure and biological profile. (PubMed, Dalton Trans) - "Fourteen cobalt(II) complexes with the non-steroidal anti-inflammatory drugs sodium meclofenamate, tolfenamic acid, mefenamic acid, naproxen, sodium diclofenac, and diflunisal were prepared in the presence or absence of a series of nitrogen-donors (namely imidazole, pyridine, 3-aminopyridine, neocuproine, 2,2'-bipyridine, 1,10-phenanthroline and 2,2'-bipyridylamine) as co-ligands and were characterised by spectroscopic and physicochemical techniques. The complexes demonstrated tight and reversible binding to human and bovine serum albumins and the binding site of bovine serum albumin was also examined. In order to assess the antioxidant activity of the compounds, the in vitro scavenging activity towards free radicals, namely 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), and their ability to reduce H2O2 were studied."

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Photolysis of tolfenamic acid in aqueous and organic solvents: a kinetic study. (PubMed, RSC Adv) - "A total of 17 photoproducts have been identified through LC-MS, of which nine have been reported for the first time. It has been confirmed through electron spin resonance (ESR) spectrometry that the excited singlet state of TA is converted into an excited triplet state through intersystem crossing, which results in an increased rate of photodegradation in acetonitrile."

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