Identification
- Summary
Niflumic acid is a cyclooxygenase-2 inhibitor used to alleviate inflammation, pain, and edema associated with acute and chronic inflammatory conditions, such as rheumatoid arthritis, osteoarthritis, post-operative inflammatory conditions, and physical trauma.
- Generic Name
- Niflumic acid
- DrugBank Accession Number
- DB04552
- Background
Niflumic acid is an analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Niflumic acid (DB04552)
- Weight
- Average: 282.218
Monoisotopic: 282.061612157 - Chemical Formula
- C13H9F3N2O2
- Synonyms
- Acide niflumique
- Acido niflumico
- Acidum niflumicum
- NFA
- Niflumic acid
- External IDs
- Lopac-N-0630
- UP 83
- UP-83
Pharmacology
- Indication
Used in the treatment of rheumatoid arthritis.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Inflammation •••••••••••• •••••••• ••••••••••• Management of Inflammation •••••••••••• •••••••• ••••••••••• Management of Inflammation •••••••••••• •••••••• ••••••••••• Management of Inflammation •••••••••••• •••••••• ••••••••••• Management of Inflammation •••••••••••• •••••••• ••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Niflumic acid, a nonsteroidal anti-inflammatory fenamate, is a Ca2+-activated Cl- channel blocker.
- Mechanism of action
Niflumic acid is able to inhibit both phospholipase A2 as well as COX-2, thereby acting as an antiinflamatory and pain reduction agent.
Target Actions Organism APhospholipase A2 inhibitorHumans AProstaglandin G/H synthase 2 inhibitorHumans UChloride channel protein ClC-Ka inducerHumans UProstaglandin G/H synthase 1 Not Available Humans UCytosolic phospholipase A2 Not Available Humans UUDP-glucuronosyltransferase 1-9 Not Available Humans - Absorption
Well absorbed following oral administration.
- Volume of distribution
Not Available
- Protein binding
90% bound to plasma proteins.
- Metabolism
Hepatic.
- Route of elimination
Not Available
- Half-life
2.5 hours
- Clearance
Not Available
- 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
Oral, mouse: LD50 = 350 mg/kg; Oral, rat: LD50 = 250 mg/kg
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 Niflumic acid 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 Niflumic acid is combined with Abciximab. Acebutolol Niflumic acid may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of adverse effects can be increased when Niflumic acid is combined with Aceclofenac. Acemetacin The risk or severity of adverse effects can be increased when Niflumic acid 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
- Niflam / Niflugel / Nifluril
Categories
- ATC Codes
- M02AA17 — Niflumic acid
- M02AA — Antiinflammatory preparations, non-steroids for topical use
- M02A — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
- M02 — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Acids, Carbocyclic
- Agents causing hyperkalemia
- Agents that produce hypertension
- Aminobenzoates
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Antiinflammatory Preparations, Non-Steroids for Topical Use
- Antirheumatic Agents
- Benzene Derivatives
- Benzoates
- Cyclooxygenase Inhibitors
- Enzyme Inhibitors
- Fenamates
- Musculo-Skeletal System
- Nephrotoxic agents
- Nicotinic Acids
- Niflumic Acid and Prodrugs
- ortho-Aminobenzoates
- Peripheral Nervous System Agents
- Pyridines
- Selective Cyclooxygenase 2 Inhibitors (NSAIDs)
- Sensory System Agents
- Topical Products for Joint and Muscular Pain
- UGT1A9 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Trifluoromethylbenzenes
- Direct Parent
- Trifluoromethylbenzenes
- Alternative Parents
- Pyridinecarboxylic acids / Aniline and substituted anilines / Aminopyridines and derivatives / Imidolactams / Vinylogous amides / Heteroaromatic compounds / Amino acids / Secondary amines / Azacyclic compounds / Carboxylic acids show 7 more
- Substituents
- Alkyl fluoride / Alkyl halide / Amine / Amino acid / Amino acid or derivatives / Aminopyridine / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle / Carboxylic acid show 20 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- pyridines, aromatic carboxylic acid (CHEBI:34888)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 4U5MP5IUD8
- CAS number
- 4394-00-7
- InChI Key
- JZFPYUNJRRFVQU-UHFFFAOYSA-N
- InChI
- InChI=1S/C13H9F3N2O2/c14-13(15,16)8-3-1-4-9(7-8)18-11-10(12(19)20)5-2-6-17-11/h1-7H,(H,17,18)(H,19,20)
- IUPAC Name
- 2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylic acid
- SMILES
- OC(=O)C1=C(NC2=CC=CC(=C2)C(F)(F)F)N=CC=C1
References
- General References
- Criddle DN, de Moura RS, Greenwood IA, Large WA: Inhibitory action of niflumic acid on noradrenaline- and 5-hydroxytryptamine-induced pressor responses in the isolated mesenteric vascular bed of the rat. Br J Pharmacol. 1997 Mar;120(5):813-8. [Article]
- External Links
- Human Metabolome Database
- HMDB0015573
- KEGG Drug
- D08275
- KEGG Compound
- C13698
- PubChem Compound
- 4488
- PubChem Substance
- 46504657
- ChemSpider
- 4333
- BindingDB
- 85507
- 7418
- ChEBI
- 34888
- ChEMBL
- CHEMBL63323
- ZINC
- ZINC000000125031
- Therapeutic Targets Database
- DAP000972
- PharmGKB
- PA164746749
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- NFL
- Wikipedia
- Niflumic_acid
- PDB Entries
- 1td7 / 2wm3 / 7ty8 / 8shc
- MSDS
- Download (73.3 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 250 MG Cream Topical Gel Topical - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 203 °C Not Available water solubility 19 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 4.43 TAKACS-NOVAK,K ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.0883 mg/mL ALOGPS logP 4.33 ALOGPS logP 3.21 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 1.88 Chemaxon pKa (Strongest Basic) 5.3 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 62.22 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 65.93 m3·mol-1 Chemaxon Polarizability 24.21 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9298 Blood Brain Barrier + 0.9115 Caco-2 permeable + 0.5318 P-glycoprotein substrate Non-substrate 0.7803 P-glycoprotein inhibitor I Non-inhibitor 0.8783 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.9236 CYP450 2C9 substrate Non-substrate 0.7654 CYP450 2D6 substrate Non-substrate 0.8881 CYP450 3A4 substrate Non-substrate 0.776 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Inhibitor 0.7762 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7812 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.8322 Biodegradation Not ready biodegradable 0.992 Rat acute toxicity 3.0838 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.988 hERG inhibition (predictor II) Non-inhibitor 0.7993
Spectra
- Mass Spec (NIST)
- Download (9.79 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 161.492864 predictedDarkChem Lite v0.1.0 [M-H]- 159.96945 predictedDeepCCS 1.0 (2019) [M+H]+ 161.710864 predictedDarkChem Lite v0.1.0 [M+H]+ 162.32745 predictedDeepCCS 1.0 (2019) [M+Na]+ 161.418464 predictedDarkChem Lite v0.1.0 [M+Na]+ 168.42061 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Receptor binding
- Specific Function
- PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides, this releases glycerophospholipids and arachidonic acid that serve as the precursors of signal molecules.
- Gene Name
- PLA2G1B
- Uniprot ID
- P04054
- Uniprot Name
- Phospholipase A2
- Molecular Weight
- 16359.535 Da
References
- Jabeen T, Singh N, Singh RK, Sharma S, Somvanshi RK, Dey S, Singh TP: Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution. Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1579-86. Epub 2005 Nov 19. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
- Jabeen T, Singh N, Singh RK, Sharma S, Somvanshi RK, Dey S, Singh TP: Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution. Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1579-86. Epub 2005 Nov 19. [Article]
- Diao HL, Zhu H, Ma H, Tan HN, Cong J, Su RW, Yang ZM: Rat ovulation, implantation and decidualization are severely compromised by COX-2 inhibitors. Front Biosci. 2007 May 1;12:3333-42. [Article]
- Alpert E, Gruzman A, Tennenbaum T, Sasson S: Selective cyclooxygenase-2 inhibitors stimulate glucose transport in L6 myotubes in a protein kinase Cdelta-dependent manner. Biochem Pharmacol. 2007 Feb 1;73(3):368-77. Epub 2006 Oct 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- 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
- Picollo A, Liantonio A, Babini E, Camerino DC, Pusch M: Mechanism of interaction of niflumic acid with heterologously expressed kidney CLC-K chloride channels. J Membr Biol. 2007 Apr;216(2-3):73-82. Epub 2007 Jul 21. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Talbot S, Lin JC, Lahjouji K, Roy JP, Senecal J, Morin A, Couture R: Cigarette smoke-induced kinin B1 receptor promotes NADPH oxidase activity in cultured human alveolar epithelial cells. Peptides. 2011 Jul;32(7):1447-56. doi: 10.1016/j.peptides.2011.05.005. Epub 2011 May 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Phospholipase a2 activity
- Specific Function
- Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory...
- Gene Name
- PLA2G4A
- Uniprot ID
- P47712
- Uniprot Name
- Cytosolic phospholipase A2
- Molecular Weight
- 85238.2 Da
References
- Jabeen T, Singh N, Singh RK, Sharma S, Somvanshi RK, Dey S, Singh TP: Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution. Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1579-86. Epub 2005 Nov 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1-9
- Molecular Weight
- 59940.495 Da
References
- Mano Y, Usui T, Kamimura H: In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid. Biopharm Drug Dispos. 2006 Jan;27(1):1-6. doi: 10.1002/bdd.475. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1-9
- Molecular Weight
- 59940.495 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Symporter activity
- Specific Function
- Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucin...
- Gene Name
- SLC16A7
- Uniprot ID
- O60669
- Uniprot Name
- Monocarboxylate transporter 2
- Molecular Weight
- 52199.745 Da
References
- Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Symporter activity
- Specific Function
- Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucin...
- Gene Name
- SLC16A1
- Uniprot ID
- P53985
- Uniprot Name
- Monocarboxylate transporter 1
- Molecular Weight
- 53943.685 Da
References
- Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. [Article]
Drug created at June 13, 2005 13:24 / Updated at June 12, 2021 10:53