Talniflumate
Identification
- Generic Name
- Talniflumate
- DrugBank Accession Number
- DB09295
- Background
Talniflumate, is an anti-inflammatory molecule studied and used as a mucin regulator in the treatment of cystic fibrosis, chronic obstructive pulmonary disease (COPD) and asthma 5. In addition, it is used in inflammatory conditions such as rheumatoid arthritis. Phase I trials with talniflumate for the treatment of cystic fibrosis and COPD were completed in August 2001, and phase II trials were performed in Ireland for the treatment of cystic fibrosis but this research has now been discontinued 7,10. Talniflumate has been approved for approximately 20 years in Argentina other countries (excluding the United States, Europe, and Japan) 10.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 414.34
Monoisotopic: 414.082741396 - Chemical Formula
- C21H13F3N2O4
- Synonyms
- Talniflumate
- Talniflumato
- Talniflumatum
- External IDs
- BA 7602-06
Pharmacology
- Indication
Talnifumate is a phthalidyl ester of nifumic acid, which has potent analgesic and anti-inflammatory effects and is widely used to treat inflammatory disorders, such as rheumatoid arthritis and osteoarthritis 13, and has also been studied for the management of cystic fibrosis 8.
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- Pharmacodynamics
Talniflumate is metabolized to its prodrug, niflumic acid, which has several pharmacodynamic effects. Firstly, it blocks synthesis of mucin. Secondly, talniflumate blocks prostaglandin synthesis by cyclooxygenases, which aids in pain and inflammation management.
- Mechanism of action
Talniflumate is a strong and selective inhibitor of core mucin-synthesizing enzyme GCNT3 (core 2 b-1,6 N-acetylglucosaminyltransferase). Talniflumate decreases gene expression of GCNT3 and production of mucins in vivo and in vitro. Talniflumate improves response of pancreatic tumors to gefitinib (chemotherapy drug). Talniflumate is a strong calcium-activated chloride channel (CaCC) blocker.
Target Actions Organism UProstaglandin G/H synthase 1 antagonistHumans UProstaglandin G/H synthase 2 antagonistHumans UChloride channel protein ClC-Ka antagonistHumans - Absorption
Not Available
- Volume of distribution
In 12 subjects after a single oral administration, total plasma clearance of the main metabolite, niflumic acid, averaged 45 ml/min giving a distribution volume of 0.12 l/kg on average 3.
- Protein binding
Niflumic acid, the active form of Talniflumate, is weak acid that is strongly bound to plasma proteins. Bioavailability was 100% in a study of 12 volunteers. It is a weak acid, strongly bound to plasma proteins 3.
- Metabolism
Extensive liver metabolism.
- Route of elimination
Not Available
- Half-life
Approximately 2h in 12 subjects 3
- Clearance
This drug undergoes extensive first pass effect.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
LD50 orally in rats: 12000 mg/kg 14
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Talniflumate may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Talniflumate is combined with Abciximab. Acebutolol Talniflumate may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of adverse effects can be increased when Aceclofenac is combined with Talniflumate. Acemetacin The risk or severity of adverse effects can be increased when Talniflumate is combined with Acemetacin. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Huluma (Myungmoon) / Somalgen / Stofen (Shin poong) / Talmain (Korea United Pharm) / Talmen (Daewoo) / Talniflumate Hanall (Hanall Biopharma) / Talumat (Taiguk) / Tariful (KWANG DONG)
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzofuranones. These are organic compounds containing a benzene ring fused to a furanone.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzofurans
- Sub Class
- Benzofuranones
- Direct Parent
- Benzofuranones
- Alternative Parents
- Trifluoromethylbenzenes / Phthalides / Pyridinecarboxylic acids / Aniline and substituted anilines / Aminopyridines and derivatives / Dicarboxylic acids and derivatives / Imidolactams / Vinylogous amides / Heteroaromatic compounds / Amino acids and derivatives show 11 more
- Substituents
- Acetal / Alkyl fluoride / Alkyl halide / Amine / Amino acid or derivatives / Aminopyridine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzenoid show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- JFK78S0U9S
- CAS number
- 66898-62-2
- InChI Key
- ANMLJLFWUCQGKZ-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H13F3N2O4/c22-21(23,24)12-5-3-6-13(11-12)26-17-16(9-4-10-25-17)19(28)30-20-15-8-2-1-7-14(15)18(27)29-20/h1-11,20H,(H,25,26)
- IUPAC Name
- 3-oxo-1,3-dihydro-2-benzofuran-1-yl 2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylate
- SMILES
- FC(F)(F)C1=CC(NC2=C(C=CC=N2)C(=O)OC2OC(=O)C3=CC=CC=C23)=CC=C1
References
- General References
- Knight D: Talniflumate (Genaera). Curr Opin Investig Drugs. 2004 May;5(5):557-62. [Article]
- Rao CV, Janakiram NB, Madka V, Kumar G, Scott EJ, Pathuri G, Bryant T, Kutche H, Zhang Y, Biddick L, Gali H, Zhao YD, Lightfoot S, Mohammed A: Small-Molecule Inhibition of GCNT3 Disrupts Mucin Biosynthesis and Malignant Cellular Behaviors in Pancreatic Cancer. Cancer Res. 2016 Apr 1;76(7):1965-74. doi: 10.1158/0008-5472.CAN-15-2820. Epub 2016 Feb 15. [Article]
- Houin G, Tremblay D, Bree F, Dufour A, Ledudal P, Tillement JP: The pharmacokinetics and availability of niflumic acid in humans. Int J Clin Pharmacol Ther Toxicol. 1983 Mar;21(3):130-4. [Article]
- Talniflumate [Link]
- Screening study for genetic polymorphisms affecting pharmacokinetics of talnifumate [Link]
- Pharmacokinetics of talniflumate, a prodrug of niflumic acid, following oral administration to man [Link]
- Talniflumate (Genaera) [Link]
- Talniflunate [Link]
- Chemistry Dashboard: Talniflumate [Link]
- TALNIFLUMATE [Link]
- Talniflumate Increases Survival in a Cystic Fibrosis Mouse Model of Distal Intestinal Obstructive Syndrome [Link]
- TALNIFLUMATE [Link]
- KWANG DONG TARIFUL TAB [Link]
- Talniflumate [Link]
- External Links
- KEGG Drug
- D02701
- PubChem Compound
- 48229
- PubChem Substance
- 310265187
- ChemSpider
- 43868
- BindingDB
- 50239971
- 236770
- ChEBI
- 91991
- ChEMBL
- CHEMBL1081506
- Drugs.com
- Drugs.com Drug Page
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 177 [L1404] boiling point (°C) 454 [L1404] water solubility 5 mg/mL clear [L1399] logP 4.47 [L1404] - Predicted Properties
Property Value Source Water Solubility 0.00417 mg/mL ALOGPS logP 4 ALOGPS logP 6.65 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 13.33 Chemaxon pKa (Strongest Basic) 3.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 77.52 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 100.11 m3·mol-1 Chemaxon Polarizability 37.83 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0090200000-300841dbed583b710ac4 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03yr-0094700000-696ffb93d4e73ec93bda Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0090200000-f5934cdb7c676f3b2b56 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03ei-0293200000-06168dd06782a53903cc Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0930000000-e81324fde1377dcb51e5 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-0950000000-93c095635f3247bb674f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 189.6018 predictedDeepCCS 1.0 (2019) [M+H]+ 191.95981 predictedDeepCCS 1.0 (2019) [M+Na]+ 198.05295 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
- Gene Name
- PTGS1
- Uniprot ID
- P23219
- Uniprot Name
- Prostaglandin G/H synthase 1
- Molecular Weight
- 68685.82 Da
References
- TALNIFLUMATE [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- TALNIFLUMATE [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Voltage-gated chloride channel activity
- Specific Function
- Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport...
- Gene Name
- CLCNKA
- Uniprot ID
- P51800
- Uniprot Name
- Chloride channel protein ClC-Ka
- Molecular Weight
- 75284.08 Da
References
- TALNIFLUMATE [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
- Gene Name
- PTGS1
- Uniprot ID
- P23219
- Uniprot Name
- Prostaglandin G/H synthase 1
- Molecular Weight
- 68685.82 Da
References
- TALNIFLUMATE [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- TALNIFLUMATE [Link]
Drug created at October 30, 2015 15:27 / Updated at February 21, 2021 18:52