Details of the Drug

General Information of Drug (ID: DMDO279)

Drug Name
Phenprocoumon
Synonyms
Falithiom; Falithrom; Fencumar; Fenprocoumona; Fenprocumon; Fenprocumone; Liquamar; Marcoumar; Marcumar; Marcuphen; Phenprocoumalol; Phenprocoumarol; Phenprocoumarole; Phenprocoumone; Phenprocoumonum; Phenprocumone; Phenprocumonum; Phenprogramma; Phenylpropylhydroxycumarinum; Fenprocumone [DCIT]; Hexal Brand of Phenprocoumon; Roche Brand of Phenprocoumon; Worwag Brand of Phenprocoumon; U29342; Falithrom (TN); Fenprocoumona [INN-Spanish]; Liquamar (TN); Marcoumar (TN); Marcumar (TN); Phenprocoumone [INN-French]; Phenprocoumonum [INN-Latin]; Ro 1-4849; Phenprocoumon (USAN/INN); Phenprocoumon [USAN:INN:BAN]; 2-hydroxy-3-(1-phenylpropyl)chromen-4-one; 3-(1'-Phenyl-propyl)-4-oxycoumarin; 3-(1'-Phenyl-propyl)-4-oxycoumarin [German]; 3-(1-Phenylpropyl)-4-hydroxycoumarin; 3-(alpha-Ethylbenzyl)-4-hydroxycoumarin; 3-(alpha-Phenylpropyl)-4-hydroxycoumarin; 4-Hydroxy-3-(1-phenylpropyl)-2H-1-benzopyran-2-one; 4-Hydroxy-3-(1-phenylpropyl)-2H-chromen-2-one
Indication
Disease Entry ICD 11 Status REF
Myocardial infarction BA41-BA43 Approved [1]
Thrombosis DB61-GB90 Approved [2]
Venous thromboembolism BD72 Investigative [1]
Therapeutic Class
Anticoagulants
Affected Organisms
Humans and other mammals
ATC Code
B01AA04: Phenprocoumon
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) 280.3
Logarithm of the Partition Coefficient (xlogp) 3.6
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Bioavailability
The bioavailability of drug is 100% []
Clearance
The drug present in the plasma can be removed from the body at the rate of 0.02 mL/min/kg [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 5 - 6 days [3]
Metabolism
The drug is metabolized via the hepatic microsomal enzymes (cytochrome P-450) to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.42691 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.57% [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 0.2 L/kg [3]
Chemical Identifiers
Formula
C18H16O3
IUPAC Name
4-hydroxy-3-(1-phenylpropyl)chromen-2-one
Canonical SMILES
CCC(C1=CC=CC=C1)C2=C(C3=CC=CC=C3OC2=O)O
InChI
InChI=1S/C18H16O3/c1-2-13(12-8-4-3-5-9-12)16-17(19)14-10-6-7-11-15(14)21-18(16)20/h3-11,13,19H,2H2,1H3
InChIKey
DQDAYGNAKTZFIW-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
54680692
ChEBI ID
CHEMBL1465
CAS Number
435-97-2
UNII
Q08SIO485D
DrugBank ID
DB00946
TTD ID
D0QV5T
VARIDT ID
DR01279
INTEDE ID
DR1279
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
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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 [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2C9 (CYP2C9)
Main DME 		DE5IED8 CP2C9_HUMAN Substrate [8]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Gene/Protein Processing [9]
Vitamin K epoxide reductase complex subunit 1 OTOJNJRD VKOR1_HUMAN Gene/Protein Processing [10]
Vitamin K epoxide reductase complex subunit 1-like protein 1 OT7QSEWT VKORL_HUMAN Gene/Protein Processing [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Phenprocoumon FDA Label
2 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: 6839).
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 [Oral anticoagulation and pharmacogenetics: importance in the clinical setting]. Rev Med Suisse. 2007 Sep 12;3(124):2030, 2033-4, 2036.
6 Role of P-glycoprotein in the uptake/efflux transport of oral vitamin K antagonists and rivaroxaban through the Caco-2 cell model. Basic Clin Pharmacol Toxicol. 2013 Oct;113(4):259-65.
7 Identification of cytochromes P450 2C9 and 3A4 as the major catalysts of phenprocoumon hydroxylation in vitro. Eur J Clin Pharmacol. 2004 May;60(3):173-82.
8 Genetic polymorphisms of cytochrome P450 2C9 causing reduced phenprocoumon (S)-7-hydroxylation in vitro and in vivo. Xenobiotica. 2004 Sep;34(9):847-59.
9 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
10 VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites. Blood Adv. 2018 Mar 27;2(6):691-702.