Details of the Drug Combination

General Information of Drug Combination (ID: DCJX8Q9)

Drug Combination Name
Phenprocoumon PF-02545920
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Phenprocoumon   DMDO279 PF-02545920   DMJPE61
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 14.08
Bliss Independence Score: 14.08
Loewe Additivity Score: 23.34
LHighest Single Agent (HSA) Score: 23.38

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Phenprocoumon
Disease Entry ICD 11 Status REF
Myocardial infarction BA41-BA43 Approved [2]
Thrombosis DB61-GB90 Approved [3]
Venous thromboembolism BD72 Investigative [2]
Phenprocoumon Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vitamin K epoxide reductase complex 1 (VKORC1) TTEUC8H VKOR1_HUMAN Inhibitor [7]
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Phenprocoumon Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Phenprocoumon Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [10]
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Phenprocoumon Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Decreases Activity [11]
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Indication(s) of PF-02545920
Disease Entry ICD 11 Status REF
Huntington disease 8A01.10 Phase 2 [4]
Schizophrenia 6A20 Phase 2 [5]
PF-02545920 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phosphodiesterase 10A (PDE10) TTJW4LU PDE10_HUMAN Inhibitor [4]
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PF-02545920 Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Lipid transferase CIDEA (CIDEA) OTDUTSOV CIDEA_HUMAN Increases Expression [12]
Type II iodothyronine deiodinase (DIO2) OTGPNSLH IOD2_HUMAN Increases Expression [12]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Increases Expression [12]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Phenprocoumon FDA Label
3 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).
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 ClinicalTrials.gov (NCT01939548) An Outpatient Study Of The Efficacy, Safety, And Tolerability Of PF-02545920 In The Adjunctive Treatment Of Sub-Optimally Controlled Symptoms of Schizophrenia. U.S. National Institutes of Health.
6 VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites. Blood Adv. 2018 Mar 27;2(6):691-702.
7 [Oral anticoagulation and pharmacogenetics: importance in the clinical setting]. Rev Med Suisse. 2007 Sep 12;3(124):2030, 2033-4, 2036.
8 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.
9 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.
10 Genetic polymorphisms of cytochrome P450 2C9 causing reduced phenprocoumon (S)-7-hydroxylation in vitro and in vivo. Xenobiotica. 2004 Sep;34(9):847-59.
11 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.
12 A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016 Jul 1;8(7):796-812. doi: 10.15252/emmm.201506085. Print 2016 Jul.