Details of the Drug

General Information of Drug (ID: DMZDF0B)

• Drug Name: Aceclofenac
• Synonyms: Airtal; Barracan; Biofenac; Bristaflam; Falcol; Gerbin; Preservex; YT-919

Indication

Disease Entry	ICD 11	Status	REF
Inflammation	1A00-CA43.1	Approved	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 354.2
  Topological Polar Surface Area (xlogp); 4.3
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.25-3 h [3]
  Clearance: The clearance of drug is 5 L/h [4]
  Elimination: The main route of elimination is via the urine where the elimination accounts for 70-80% of clearance of the drug [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 4 hours [3]
  Metabolism: The drug is metabolized via plasma [5]
  Vd: The volume of distribution (Vd) of drug is 25 L [3]
• Chemical Identifiers:
  Formula: C16H13Cl2NO4
  IUPAC Name: 2-[2-[2-(2,6-dichloroanilino)phenyl]acetyl]oxyacetic acid
  Canonical SMILES: C1=CC=C(C(=C1)CC(=O)OCC(=O)O)NC2=C(C=CC=C2Cl)Cl
  InChI: InChI=1S/C16H13Cl2NO4/c17-11-5-3-6-12(18)16(11)19-13-7-2-1-4-10(13)8-15(22)23-9-14(20)21/h1-7,19H,8-9H2,(H,20,21)
  InChIKey: MNIPYSSQXLZQLJ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 71771
  ChEBI ID: CHEBI:31159
  CAS Number: 89796-99-6
  DrugBank ID: DB06736
  TTD ID: D0T8VY
  INTEDE ID: DR0033

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin G/H synthase (COX)	TTK0943	PGH1_HUMAN; PGH2_HUMAN	Modulator	[6], [1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[7]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] ClinicalTrials.gov (NCT01912066) A Multicenter, Double Blinded, Randomized, Parallel Assignment Study to Demonstrate the Efficacy of DA9601. U.S. National Institutes of Health.
• [3] UK Medicines and Healthcare products Regulatory Agency: ACECLOFENAC 100MG TABLETS product information
• [4] Ghosh S, Barik BB: A Comparative Study of the Pharmacokinetics of Conventional and Sustained-release Tablet Formulations of Aceclofenac in Healthy Male Subjects Tropical Journal of Pharmaceutical Research. 2010 September 1;9(4):395-399.
• [5] Mahajan MK, Uttamsingh V, Daniels JS, Gan LS, LeDuc BW, Williams DA: In vitro metabolism of oxymetazoline: evidence for bioactivation to a reactive metabolite. Drug Metab Dispos. 2011 Apr;39(4):693-702. doi: 10.1124/dmd.110.036004. Epub 2010 Dec 21.
• [6] Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35.
• [7] Metabolism of aceclofenac in humans. Drug Metab Dispos. 1996 Aug;24(8):834-41.
• [8] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [9] Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
• [10] Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
• [11] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [12] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [13] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [14] New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
• [15] A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
• [16] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [17] Mechanism of action of paracetamol. Am J Ther. 2005 Jan-Feb;12(1):46-55.
• [18] Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. Urol Res. 2000 Dec;28(6):376-82.
• [19] Cyclooxygenase inhibitors: instrumental drugs to understand cardiovascular homeostasis and arterial thrombosis. Cardiovasc Hematol Disord Drug Targets. 2008 Dec;8(4):268-77.
• [20] Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip. Int J Clin Pharmacol Ther. 2003 Apr;41(4):153-64.
• [21] Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H425-32.
• [22] Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. Ann N Y Acad Sci. 1994 Nov 15;744:50-7.
• [23] The aryl propionic acid R-flurbiprofen selectively induces p75NTR-dependent decreased survival of prostate tumor cells. Cancer Res. 2007 Apr 1;67(7):3254-62.
• [24] The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res. 1999 Jul;48(7):369-79.
• [25] Modulation of arachidonic acid metabolism by orally administered morniflumate in man. Agents Actions. 1991 Jul;33(3-4):233-9.
• [26] Topical nepafenac inhibits ocular neovascularization. Invest Ophthalmol Vis Sci. 2003 Jan;44(1):409-15.