Details of the Drug

General Information of Drug (ID: DM8J0MK)

Drug Name
GEA-6414
Synonyms
Tolfenamic acid; Acide tolfenamique; Acido tolfenamico; Acidum tolfenamicum; Bifenac; Clotam; GEA 6414; Tolfedine; tolfenamic acid; 13710-19-5; 2-(3-Chloro-2-methylanilino)benzoic acid; 2-[(3-Chloro-2-methylphenyl)amino]benzoic Acid; 3G943U18KM; Anthranilic acid, N-(3-chloro-o-tolyl)-; Benzoic acid, 2-[(3-chloro-2-methylphenyl)amino]-; CAS-13710-19-5; CHEBI:32243; N-(2-Methyl-3-chlorophenyl)anthranilic acid; N-(3-Chloro-2-methylphenyl)anthranilic acid; N-(3-Chloro-o-tolyl)-anthranilic acid; NCGC00016705-05; UNII-3G943U18KM
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 261.7
Logarithm of the Partition Coefficient (xlogp) 5.2
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 5 h []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [1]
Bioavailability
The bioavailability of drug is 48% []
Clearance
The drug present in the plasma can be removed from the body at the rate of 2.37 mL/min/kg [2]
Elimination
Most of the elimination occurs by extrarenal mechanisms in which the unchanged drug together with its glucuronide in urine accounts for only 8.8% of the administered dose [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 8.01 - 13.50 hours [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 21.8344 micromolar/kg/day [5]
Unbound Fraction
The unbound fraction of drug in plasma is 0.003% [2]
Vd
The volume of distribution (Vd) of drug is 1.79-3.2 L/kg [4]
Chemical Identifiers
Formula
C14H12ClNO2
IUPAC Name
2-(3-chloro-2-methylanilino)benzoic acid
Canonical SMILES
CC1=C(C=CC=C1Cl)NC2=CC=CC=C2C(=O)O
InChI
YEZNLOUZAIOMLT-UHFFFAOYSA-N
InChIKey
1S/C14H12ClNO2/c1-9-11(15)6-4-8-12(9)16-13-7-3-2-5-10(13)14(17)18/h2-8,16H,1H3,(H,17,18)
Cross-matching ID
PubChem CID
610479
ChEBI ID
CHEBI:32243
CAS Number
13710-19-5
DrugBank ID
DB09216
INTEDE ID
DR1613

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Gene/Protein Processing [8]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Gene/Protein Processing [9]
Proteasome subunit beta type-10 (PSMB10) OTURUR9B PSB10_HUMAN Gene/Protein Processing [10]
Proteasome subunit beta type-9 (PSMB9) OTFV57T8 PSB9_HUMAN Gene/Protein Processing [10]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Gene/Protein Processing [11]
TGF-beta receptor type-2 (TGFBR2) OT3P7GZP TGFR2_HUMAN Gene/Protein Processing [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 BDDCS applied to over 900 drugs
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 Pedersen SB: Biopharmaceutical aspects of tolfenamic acid. Pharmacol Toxicol. 1994;75 Suppl 2:22-32.
4 Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation. Vet J. 1998 May;155(3):275-88.
5 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6 Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
7 Both reactivity and accessibility are important in cytochrome P450 metabolism: a combined DFT and MD study of fenamic acids in BM3 mutants. J Chem Inf Model. 2019 Feb 25;59(2):743-753.
8 Roles of rat and human aldo-keto reductases in metabolism of farnesol and geranylgeraniol. Chem Biol Interact. 2011 May 30;191(1-3):261-8. doi: 10.1016/j.cbi.2010.12.017. Epub 2010 Dec 25.
9 Tolfenamic acid is a potent CYP1A2 inhibitor in vitro but does not interact in vivo: correction for protein binding is needed for data interpretation. Eur J Clin Pharmacol. 2007 Sep;63(9):829-36. doi: 10.1007/s00228-007-0335-z. Epub 2007 Jul 6.
10 Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers. Chem Biol Interact. 2013 Feb 25;202(1-3):234-42.
11 The involvement of lipid raft pathway in suppression of TGF-mediated metastasis by tolfenamic acid in hepatocellular carcinoma cells. Toxicol Appl Pharmacol. 2019 Oct 1;380:114696. doi: 10.1016/j.taap.2019.114696. Epub 2019 Aug 2.