Details of the Drug

General Information of Drug (ID: DM7APNJ)

• Drug Name: Zomepirac
• Synonyms: ZOMEPIRAC SODIUM; Zomepirac sodium [USAN:USP]; UNII-Y0185WZ209; McN-2783-21-98; Y0185WZ209; 64092-49-5; Zomepirac sodium dihydrate; 1H-Pyrrole-2-acetic acid, 5-(4-chlorobenzoyl)-1,4-dimethyl-, sodium salt, dihydrate; Zomepirac sodium (USAN); CHEMBL3989403; DTXSID60214282; ZJXLSCXDGPDZOL-UHFFFAOYSA-M; D06382; Sodium 5-(p-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate dihydrate; Sodium 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetate Dihydrate

Indication

Disease Entry	ICD 11	Status	REF
Pain	MG30-MG3Z	Withdrawn from market	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 291.73
  Topological Polar Surface Area (xlogp); 2.8
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property: BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
• Chemical Identifiers:
  Formula: C15H14ClNO3
  IUPAC Name: 2-[5-(4-chlorobenzoyl)-1,4-dimethylpyrrol-2-yl]acetic acid
  Canonical SMILES: CC1=C(N(C(=C1)CC(=O)O)C)C(=O)C2=CC=C(C=C2)Cl
  InChI: InChI=1S/C15H14ClNO3/c1-9-7-12(8-13(18)19)17(2)14(9)15(20)10-3-5-11(16)6-4-10/h3-7H,8H2,1-2H3,(H,18,19)
  InChIKey: ZXVNMYWKKDOREA-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5733
  ChEBI ID: CHEBI:35859
  CAS Number: 33369-31-2
  DrugBank ID: DB04828
  TTD ID: D0SU1G
  INTEDE ID: DR1736

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	[3], [1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [3] Effect of preischemia cyclooxygenase inhibition by zomepirac sodium on reflow, cerebral autoregulation, and EEG recovery in the cat after global ischemia. J Cereb Blood Flow Metab. 1986 Dec;6(6):691-702.
• [4] Evidence for the bioactivation of zomepirac and tolmetin by an oxidative pathway: identification of glutathione adducts in vitro in human liver microsomes and in vivo in rats. Drug Metab Dispos. 2006 Jan;34(1):145-51.
• [5] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [6] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [7] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [8] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [9] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [10] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [11] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [12] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [13] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [14] Mechanism of action of paracetamol. Am J Ther. 2005 Jan-Feb;12(1):46-55.
• [15] 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.
• [16] Cyclooxygenase inhibitors: instrumental drugs to understand cardiovascular homeostasis and arterial thrombosis. Cardiovasc Hematol Disord Drug Targets. 2008 Dec;8(4):268-77.
• [17] 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.
• [18] Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H425-32.
• [19] Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. Ann N Y Acad Sci. 1994 Nov 15;744:50-7.
• [20] 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.
• [21] Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35.
• [22] 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.
• [23] Modulation of arachidonic acid metabolism by orally administered morniflumate in man. Agents Actions. 1991 Jul;33(3-4):233-9.