Identification

Name
Talniflumate
Accession Number
DB09295
Type
Small Molecule
Groups
Experimental
Description

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].

Structure
Thumb
Synonyms
Not Available
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
UNII
JFK78S0U9S
CAS number
66898-62-2
Weight
Average: 414.34
Monoisotopic: 414.082741396
Chemical Formula
C21H13F3N2O4
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

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].

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.

TargetActionsOrganism
UProstaglandin G/H synthase 1
antagonist
Human
UProstaglandin G/H synthase 2
antagonist
Human
UChloride channel protein ClC-Ka
antagonist
Human
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.

Toxicity

LD50 orally in rats: 12000 mg/kg [14]

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when Talniflumate is combined with (4R)-limonene.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Talniflumate.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Talniflumate.
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Talniflumate.
AcebutololTalniflumate may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Talniflumate is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Talniflumate is combined with Acemetacin.
AcetaminophenTalniflumate may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcyclovirTalniflumate may decrease the excretion rate of Acyclovir which could result in a higher serum level.
Adefovir DipivoxilThe risk or severity of nephrotoxicity can be increased when Talniflumate is combined with Adefovir Dipivoxil.
Food Interactions
Not Available

References

General References
  1. Knight D: Talniflumate (Genaera). Curr Opin Investig Drugs. 2004 May;5(5):557-62. [PubMed:15202731]
  2. 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. [PubMed:26880801]
  3. 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. [PubMed:6852999]
  4. Talniflumate [Link]
  5. Screening study for genetic polymorphisms af­fecting pharmacokinetics of talnifumate [Link]
  6. Pharmacokinetics of talniflumate, a prodrug of niflumic acid, following oral administration to man [Link]
  7. Talniflumate (Genaera) [Link]
  8. Talniflunate [Link]
  9. Chemistry Dashboard: Talniflumate [Link]
  10. TALNIFLUMATE [Link]
  11. Talniflumate Increases Survival in a Cystic Fibrosis Mouse Model of Distal Intestinal Obstructive Syndrome [Link]
  12. TALNIFLUMATE [Link]
  13. KWANG DONG TARIFUL TAB [Link]
  14. Talniflumate [Link]
External Links
KEGG Drug
D02701
PubChem Compound
48229
PubChem Substance
310265187
ChemSpider
43868
ChEBI
91991
ChEMBL
CHEMBL1081506
Drugs.com
Drugs.com Drug Page

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)177[L1404]
boiling point (°C)454[L1404]
water solubility5 mg/mL clear[L1399]
logP4.47[L1404]
Predicted Properties
PropertyValueSource
Water Solubility0.00417 mg/mLALOGPS
logP4ALOGPS
logP6.65ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)13.33ChemAxon
pKa (Strongest Basic)3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.52 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity100.11 m3·mol-1ChemAxon
Polarizability37.83 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Trifluoromethylbenzene / Benzofuranone / Isobenzofuranone / Phthalide / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Isocoumaran / Aniline or substituted anilines / Aminopyridine / Monocyclic benzene moiety
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
  1. TALNIFLUMATE [Link]
Kind
Protein
Organism
Human
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
  1. TALNIFLUMATE [Link]
Kind
Protein
Organism
Human
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
  1. TALNIFLUMATE [Link]

Enzymes

Kind
Protein
Organism
Human
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
  1. TALNIFLUMATE [Link]
Kind
Protein
Organism
Human
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
  1. TALNIFLUMATE [Link]

Drug created on October 30, 2015 09:27 / Updated on October 01, 2018 14:49