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
CHEBI:50438
CAS Number
435-97-2
UNII
Q08SIO485D
DrugBank ID
DB00946
TTD ID
D0QV5T
VARIDT ID
DR01279
INTEDE ID
DR1279
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD 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 [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.