Details of the Drug Combination

General Information of Drug Combination (ID: DC1HT2Z)

• Drug Combination Name: GINKGOLIDE A + Phenprocoumon
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  GINKGOLIDE A (DMKZJ7T): Small molecular drug
  Phenprocoumon (DMDO279): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 24.04
  Bliss Independence Score: 24.04
  Loewe Additivity Score: 40.98
  LHighest Single Agent (HSA) Score: 40.99

Molecular Interaction Atlas of This Drug Combination

Indication(s) of GINKGOLIDE A

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

GINKGOLIDE A Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Strychnine-binding glycine receptor (GLRA1)	TTF45NW	GLRA1_HUMAN	Inhibitor	[6]
Glycine receptor (GlyR)	TTZ8EM9	GLRA1_HUMAN; GLRA2_HUMAN; GLRA3_HUMAN; GLRA4_HUMAN; GLRB_HUMAN	Inhibitor	[6]

GINKGOLIDE A Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[5]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[5]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[5]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[5]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[5]

Indication(s) of Phenprocoumon

Disease Entry	ICD 11	Status	REF
Myocardial infarction	BA41-BA43	Approved	[3]
Thrombosis	DB61-GB90	Approved	[4]
Venous thromboembolism	BD72	Investigative	[3]

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	[8]

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	[9]

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	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[10]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[11]

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	[12]

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] 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: 1861).
• [3] Phenprocoumon FDA Label
• [4] 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).
• [5] Bioactive terpenoids and flavonoids from Ginkgo biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor-mediated pathways. Pharm Res. 2009 Apr;26(4):872-82.
• [6] Probing the pharmacophore of ginkgolides as glycine receptor antagonists. J Med Chem. 2007 Apr 5;50(7):1610-7.
• [7] VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites. Blood Adv. 2018 Mar 27;2(6):691-702.
• [8] [Oral anticoagulation and pharmacogenetics: importance in the clinical setting]. Rev Med Suisse. 2007 Sep 12;3(124):2030, 2033-4, 2036.
• [9] 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.
• [10] 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.
• [11] Genetic polymorphisms of cytochrome P450 2C9 causing reduced phenprocoumon (S)-7-hydroxylation in vitro and in vivo. Xenobiotica. 2004 Sep;34(9):847-59.
• [12] 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.