Details of the Drug

General Information of Drug (ID: DMH75KV)

Drug Name
Acenocoumarol
Synonyms
Acenocoumarin; Acenocoumarolum; Acenocumarol; Acenocumarolo; Acenocumarolum; Acenokumarin; Ascumar; Minisintrom; Neositron;Nicoumalone; Nicumalon; Nitrovarfarian; Nitrowarfarin; Sincoumar; Sinkumar; Sinthrom; Sinthrome; Sintrom; Sintroma; Syncoumar; Syncumar; Synthrom; Syntrom; Zotil; Acenocoumarol Alliance Brand; Acenocoumarol Novartis Brand; Acenocoumarol [INN]; Acenocumarolo [DCIT]; Acenokumarin [Czech]; Alliance Brand of Acenocoumarol; Ciba Geigy Brand of Acenocoumarol; Mini Sintrom; Novartis Brand of Acenocoumarol; G 23350; Acenocoumarol (INN); Acenocoumarol Ciba-Geigy Brand; Acenocoumarolum [INN-Latin]; Ciba-Geigy Brand of Acenocoumarol; G-23350; Mini-sintrom; Sinthrome (TN); Sintrom (TN); AB-014/25000129; G-23,350; Mini-sintrom (TN); Nitrophenylacetylethyl-4-hydroxycoumarine; 2-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-4h-chromen-4-one; 2-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]chromen-4-one; 3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarin; 3-(alpha-(p-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarin; 3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin; 3-(alpha-Acetonyl-p-nitrobenzyl)-4-hydroxycoumarin; 3-(alpha-Acetonyl-para-nitrobenzyl)-4-hydroxy-coumarin; 3-(alpha-p-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarin; 4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-one;4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
Indication
Disease Entry ICD 11 Status REF
Thrombosis DB61-GB90 Approved [1]
Therapeutic Class
Anticoagulants
Affected Organisms
Humans and other mammals
ATC Code
B01AA07: Acenocoumarol
B01AA: Vitamin K antagonists
B01A: ANTITHROMBOTIC AGENTS
B01: ANTITHROMBOTIC AGENTS
B: BLOOD AND BLOOD FORMING ORGANS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 353.3
Logarithm of the Partition Coefficient (xlogp) 2.5
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Bioavailability
The bioavailability of drug is 60% []
Clearance
The drug present in the plasma can be removed from the body at the rate of 1.28 mL/min/kg [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 8 - 11 hours [2]
Metabolism
The drug is metabolized via the liver []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.56604 micromolar/kg/day [3]
Unbound Fraction
The unbound fraction of drug in plasma is 0.02% [2]
Vd
The volume of distribution (Vd) of drug is 0.078 L/kg []
Chemical Identifiers
Formula
C19H15NO6
IUPAC Name
4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]chromen-2-one
Canonical SMILES
CC(=O)CC(C1=CC=C(C=C1)[N+](=O)[O-])C2=C(C3=CC=CC=C3OC2=O)O
InChI
InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3
InChIKey
VABCILAOYCMVPS-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
54676537
ChEBI ID
CHEBI:53766
CAS Number
152-72-7
UNII
I6WP63U32H
DrugBank ID
DB01418
TTD ID
D05HFY
INTEDE ID
DR0036
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Vitamin K epoxide reductase complex 1 (VKORC1) TTEUC8H VKOR1_HUMAN Inhibitor [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [5]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [6]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [7]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Drug Response [8]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Drug Response [9]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Regulation of Drug Effects [10]
Cytochrome P450 2C18 (CYP2C18) OTY687L9 CP2CI_HUMAN Drug Response [11]
Cytochrome P450 4F2 (CYP4F2) OTKILAER CP4F2_HUMAN Drug Response [11]
Vitamin K epoxide reductase complex subunit 1 OTOJNJRD VKOR1_HUMAN Drug Response [12]
Vitamin K epoxide reductase complex subunit 1-like protein 1 OT7QSEWT VKORL_HUMAN Gene/Protein Processing [13]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Drug information of Acenocoumarol, 2008. eduDrugs.
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 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
4 Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity. Mol Biol Rep. 2010 Apr;37(4):1693-7.
5 Possible interaction between topical terbinafine and acenocoumarol. Ann Pharmacother. 2009 Nov;43(11):1911-2.
6 Prediction of pharmacokinetic drug/drug interactions from In vitro data: interactions of the nonsteroidal anti-inflammatory drug lornoxicam with oral anticoagulants. Drug Metab Dispos. 2000 Feb;28(2):161-8.
7 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.
8 Patients with an ApoE epsilon4 allele require lower doses of coumarin anticoagulants. Pharmacogenet Genomics. 2005 Feb;15(2):69-74. doi: 10.1097/01213011-200502000-00002.
9 Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9.
10 Severe interaction between ritonavir and acenocoumarol. Ann Pharmacother. 2002 Apr;36(4):621-3.
11 A genome-wide association study of acenocoumarol maintenance dosage. Hum Mol Genet. 2009 Oct 1;18(19):3758-68. doi: 10.1093/hmg/ddp309. Epub 2009 Jul 4.
12 A vitamin K epoxide reductase-oxidase complex gene polymorphism (-1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists. J Appl Genet. 2009;50(4):399-403. doi: 10.1007/BF03195700.
13 VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites. Blood Adv. 2018 Mar 27;2(6):691-702.