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]
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Therapeutic Class

Anticoagulants

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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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
DrugBank ID: DB01418
TTD ID: D05HFY
INTEDE ID: DR0036

Combinatorial Drugs (CBD)

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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]

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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]

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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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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.