Details of the Drug

General Information of Drug (ID: DMJ3I1Q)

• Drug Name: Niflumic acid
• Synonyms: Actol; Donalgin; Flunir; Forenol; Landruma; NFL; Niflactol; Niflam; Niflugel; Niflumate; Nifluril; Acide niflumique; Acide niflumique [French]; Acido niflumico; Acido niflumico [Italian]; Acidum niflumicum; Nifluminic acid; UPSA Conseil Brand of Niflumic Acid; Upsamedica Brand of Niflumic Acid; N 0630; SC 1332; UP 83; UPSA Brand 1 of Niflumic Acid; UPSA Brand 2 of Niflumic Acid; Acid, Niflumic; Acide niflumique [INN-French]; Acido niflumico [INN-Spanish]; Acidum niflumicum [INN-Latin]; Niflugel (TN); Niflumic acid (INN); Niflumic acid [INN:DCF]; Aza-2 dimethyl-2',3' (tetrazolyl-5)-6 diphenylamino; Aza-2 dimethyl-2',3' (tetrazolyl-5)-6 diphenylamino [French]; 2-(3-(Trifluoromethyl)-phenyl)aminonicotinic acid; 2-(3-(Trifluoromethyl)anilino)nicotinic acid; 2-(3-Trifluoromethyl-phenylamino)-nicotinic acid; 2-(3-Trifluoromethylanilino)nicotinic Acid; 2-(3-[Trifluoromethyl]anilino)nicotinic acid; 2-(A,A,A-Trifluoro-m-toluidino)nicotinic acid; 2-(alpha,alpha,alpha-Trifluoro-m-toluidino)nicotinic acid; 2-[(3-TRIFLUOROMETHYL)PHENYL]AMINO-3-PYRIDINE-CARBOXYLIC ACID; 2-[(3-Trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic Acid; 2-[(3-Trifluoromethylphenyl)amino]nicotinic Acid; 2-[3-(Trifluoromethyl)anilino]nicotinic acid; 2-[3-(trifluoromethyl)anilino]pyridine-3-carboxylic acid; 2-[alpha,alpha,alpha-trifluoro-m-toluidino]-nicotinic acid; 2-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}NICOTINIC ACID; 2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylic acid; 39690A

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Approved	[1], [2], [3]

• Therapeutic Class: Antiinflammatory Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 282.22
  Topological Polar Surface Area (xlogp); 3.7
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption: The drug is well absorbed after oral administration [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.5 hours [5]
  Metabolism: The drug is metabolized via the hepatic [4]
• Chemical Identifiers:
  Formula: C13H9F3N2O2
  IUPAC Name: 2-[3-(trifluoromethyl)anilino]pyridine-3-carboxylic acid
  Canonical SMILES: C1=CC(=CC(=C1)NC2=C(C=CC=N2)C(=O)O)C(F)(F)F
  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)
  InChIKey: JZFPYUNJRRFVQU-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4488
  ChEBI ID: CHEBI:34888
  CAS Number: 4394-00-7
  DrugBank ID: DB04552
  TTD ID: D00HGB
  VARIDT ID: DR01158
  INTEDE ID: DR1153

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME	DEYGVN4	UD11_HUMAN	Substrate	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Rheumatoid arthritis
• ICD Disease Classification: FA20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin G/H synthase 2 (COX-2)	DTT	PTGS2	7.93E-04	-0.29	-0.34
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	1.10E-01	-5.91E-02	-3.60E-01

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2439).
• [2] Drug information of Niflumic Acid, 2008. eduDrugs.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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• [14] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [15] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [16] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [17] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
• [18] Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
• [19] Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000 Oct;40(10):1109-20.
• [20] Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis. Intern Med. 2007;46(13):1055-8.
• [21] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [22] Pfizer. Product Development Pipeline. March 31 2009.
• [23] Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo. Exp Nephrol. 2001;9(6):387-96.
• [24] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [25] Flurbiprofen, a cyclooxygenase inhibitor, protects mice from hepatic ischemia/reperfusion injury by inhibiting GSK-3 signaling and mitochondrial permeability transition.Mol Med.2012 Sep 25;18:1128-35.
• [26] Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.