Details of the Drug

General Information of Drug (ID: DMRQAM0)

Drug Name
Phenacetin
Synonyms
phenacetin; 62-44-2; Acetophenetidin; N-(4-Ethoxyphenyl)acetamide; Acetphenetidin; Acetophenetidine; Acetophenetin; Phenacetine; p-Acetophenetidide; Contradouleur; Commotional; Achrocidin; Phenazetin; Contradol; Codempiral; 4'-Ethoxyacetanilide; 4-Ethoxyacetanilide; Acetamide, N-(4-ethoxyphenyl)-; p-Acetophenetidine; Fenacetina; Phenidin; Pyraphen; Phenacitin; Phenacetinum; Fenidina; Phenedina; Phenacet; Pertonal; Fenina; Phenin; Kalmin; p-Acetphenetidin; p-Acetophenetide; Phenazetina; Tetracydin; p-Ethoxyacetanilide; Stellacyl; Phenodyne; Imidazo[4,5-e][1,4]diazapine nucleotide (I)
Indication
Disease Entry ICD 11 Status REF
Analgesia MB40.8 Withdrawn from market [1]
Affected Organisms
Humans and other mammals
ATC Code
N02BE03: Phenacetin
N02BE: Anilides
N02B: OTHER ANALGESICS AND ANTIPYRETICS
N02: ANALGESICS
N: NERVOUS SYSTEM
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 179.22
Logarithm of the Partition Coefficient (xlogp) 1.6
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Clearance
The drug present in the plasma can be removed from the body at the rate of 21 mL/min/kg [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 0.92 hours [3]
Metabolism
The drug is metabolized via the the body to paracetamol []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 278.98578 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.47% [3]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.4 L/kg [3]
Water Solubility
The ability of drug to dissolve in water is measured as 0.73 mg/mL [2]
Chemical Identifiers
Formula
C10H13NO2
IUPAC Name
N-(4-ethoxyphenyl)acetamide
Canonical SMILES
CCOC1=CC=C(C=C1)NC(=O)C
InChI
InChI=1S/C10H13NO2/c1-3-13-10-6-4-9(5-7-10)11-8(2)12/h4-7H,3H2,1-2H3,(H,11,12)
InChIKey
CPJSUEIXXCENMM-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4754
ChEBI ID
CHEBI:8050
CAS Number
62-44-2
UNII
ER0CTH01H9
DrugBank ID
DB03783
TTD ID
D0O2IE
VARIDT ID
DR00653
INTEDE ID
DR1270

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TTL7C8Q IMDH1_HUMAN Inhibitor [5]
Prostaglandin G/H synthase 1 (COX-1) TT8NGED PGH1_HUMAN Inhibitor [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [8]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [9]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [9]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [11]
Cytochrome P450 2A13 (CYP2A13) DEXZA9U CP2AD_HUMAN Substrate [11]
Cholesterol 24-hydroxylase (CYP46A1) DEKP5HX CP46A_HUMAN Substrate [12]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Arylacetamide deacetylase (AADAC) OT8VACT2 AAAD_HUMAN Biotransformations [13]
Cholesterol 24-hydroxylase (CYP46A1) OTJ27FOX CP46A_HUMAN Biotransformations [12]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Biotransformations [14]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Gene/Protein Processing [15]
Prostaglandin G/H synthase 1 (PTGS1) OTHCRLEC PGH1_HUMAN Gene/Protein Processing [16]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Gene/Protein Processing [15]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Gene/Protein Processing [15]
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Gene/Protein Processing [15]
Xaa-Pro dipeptidase (PEPD) OT3LFY7S PEPD_HUMAN Gene/Protein Processing [17]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Analgesia
ICD Disease Classification MB40.8
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Prostaglandin G/H synthase 1 (COX-1) DTT PTGS1 3.97E-03 0.16 0.43
Cytochrome P450 2A13 (CYP2A13) DME CYP2A13 9.89E-01 -6.41E-03 -3.83E-02
Cytochrome P450 2E1 (CYP2E1) DME CYP2E1 1.87E-04 -1.20E-01 -3.22E-01
Cholesterol 24-hydroxylase (CYP46A1) DME CYP46A1 1.79E-06 -3.32E-01 -6.53E-01
Cytochrome P450 2A6 (CYP2A6) DME CYP2A6 2.02E-01 -2.49E-02 -1.81E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.36E-01 1.62E-02 1.08E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 2.40E-01 -3.31E-02 -1.97E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 7.30E-01 -1.91E-02 -1.41E-01
Cytochrome P450 1A1 (CYP1A1) DME CYP1A1 6.83E-06 -1.42E-01 -4.93E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 1.90E-01 -9.81E-03 -5.96E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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: 7402).
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 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
5 A potent "fat base" nucleotide inhibitor of IMP dehydrogenase. Biochemistry. 1998 Aug 25;37(34):11949-52.
6 Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5317-22.
7 Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes. Drug Metab Dispos. 1999 Aug;27(8):860-5.
8 Human cytochromes P450 mediating phenacetin O-deethylation in vitro: validation of the high affinity component as an index of CYP1A2 activity. J Pharm Sci. 1998 Dec;87(12):1502-7.
9 Activation of phenacetin O-deethylase activity by alpha-naphthoflavone in human liver microsomes. Xenobiotica. 1999 Sep;29(9):885-98.
10 Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans. Drug Metab Dispos. 2000 Aug;28(8):937-44.
11 CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline. Drug Metab Dispos. 2007 Mar;35(3):335-9.
12 Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
13 Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse. Drug Metab Dispos. 2012 Apr;40(4):671-9. doi: 10.1124/dmd.111.043067. Epub 2011 Dec 29.
14 A population approach to enzyme characterization and identification: application to phenacetin O-deethylation. Pharm Res. 2000 Dec;17(12):1531-6. doi: 10.1023/a:1007665310830.
15 Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 2002 Nov;303(2):534-9.
16 Cloning, expression, and functional characterization of human cyclooxygenase-1 splicing variants: evidence for intron 1 retention. J Pharmacol Exp Ther. 2005 Dec;315(3):1298-305.
17 Kinetic study of paracetamol on prolidase activity in erythrocytes by capillary electrophoresis with Ru(bpy)(3) (2+) electrochemiluminescence detection. Electrophoresis. 2006 Oct;27(20):4047-51. doi: 10.1002/elps.200600197.