Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMN6EZY)

Drug Name

Vitamin K Drug Info

Synonyms

12001-79-5; MBWXNTAXLNYFJB-LKUDQCMESA-N; 81818-54-4

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

Cross-matching ID

PubChem CID: 5280483
ChEBI ID: CHEBI:94399
CAS Number: CAS 12001-79-5
TTD Drug ID: DMN6EZY
INTEDE Drug ID: DR1702

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

DOT

Drug Status:

Approved Drug(s)

Download the Complete Related Drug List

Drug(s) Targeting Coagulation factor IIa (F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Argatroban	DMFI46A	Thrombosis	DB61-GB90	Approved	[8]
Pyridoxal Phosphate	DMO2K0J	Malnutrition	5B50-5B71	Approved	[9]
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[10]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[11]
Dabigatran	DMDI6R4	Stroke	8B20	Approved	[12]
Desirudin Recombinant	DM2BTFN	Coagulation defect	3B10.0	Approved	[13]
Human prothrombin complex concentrate	DMPHVQ1	Bleeding disorder	GA20-GA21	Approved	[14]
Lepirudin	DM1I3D5	Thrombocytopenia	3B64	Approved	[15]
Anisindione	DM2C48U	Coagulation defect	3B10.0	Approved	[16]
ATryn antithrombin	DM79Y2T	Multiple sclerosis	8A40	Approved	[17]
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Drug(s) Metabolized By Vitamin K1 2,3-epoxide reductase 1 (VKOR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Menadiol sodium diphosphate	DMP9N85	Coagulation defect	3B10.0	Approved	[18]
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Drug(s) Affected By Tyrosine-protein kinase receptor UFO (AXL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[19]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[20]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[21]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[22]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[20]
Plicamycin	DM7C8YV	Hypercalcaemia	5B91.0	Approved	[23]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[24]
Clodronate	DM9Y6X7	Hypercalcaemia	5B91.0	Approved	[25]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[25]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[25]
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Drug(s) Affected By Apolipoprotein E (APOE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[26]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[27]
Selenium	DM25CGV	N. A.	N. A.	Approved	[19]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[22]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[28]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[30]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[31]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[32]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[33]
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Drug(s) Affected By Cytochrome P450 4F2 (CYP4F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Warfarin	DMJYCVW	Atrial fibrillation	BC81.3	Approved	[34]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[35]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[36]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[37]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[33]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[38]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[39]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[35]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[40]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[33]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Coagulation factor IIa (F2)	TT6L509	THRB_HUMAN	Cofactor	[1]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Vitamin K1 2,3-epoxide reductase 1 (VKOR)	DEVRYQN	VKOR1_HUMAN	Substrate	[2]
VKORC1-like protein 1 (VKORC1L1)	DERQV72	VKORL_HUMAN	Substrate	[3]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Regulation of Drug Effects	[4]
Cytochrome P450 4F2 (CYP4F2)	OTKILAER	CP4F2_HUMAN	Regulation of Drug Effects	[5]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Gene/Protein Processing	[6]
UbiA prenyltransferase domain-containing protein 1	OTRUQ2N8	UBIA1_HUMAN	Regulation of Drug Effects	[7]

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References

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2	VKORC1L1, an enzyme mediating the effect of vitamin K in liver and extrahepatic tissues. Nutrients. 2018 Jul 26;10(8). pii: E970.
3	VKORC1L1, an enzyme rescuing the vitamin K 2,3-epoxide reductase activity in some extrahepatic tissues during anticoagulation therapy. J Biol Chem. 2013 Oct 4;288(40):28733-42.
4	Warfarin dose related to apolipoprotein E (APOE) genotype. Eur J Clin Pharmacol. 2005 Jul;61(5-6):381-8. doi: 10.1007/s00228-005-0936-3. Epub 2005 Jun 11.
5	Effects of CYP4F2 genetic polymorphisms and haplotypes on clinical outcomes in patients initiated on warfarin therapy. Pharmacogenet Genomics. 2009 Oct;19(10):781-9. doi: 10.1097/FPC.0b013e3283311347.
6	Warfarin Blocks Gas6-Mediated Axl Activation Required for Pancreatic Cancer Epithelial Plasticity and Metastasis. Cancer Res. 2015 Sep 15;75(18):3699-705. doi: 10.1158/0008-5472.CAN-14-2887-T. Epub 2015 Jul 23.
7	Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature. 2010 Nov 4;468(7320):117-21. doi: 10.1038/nature09464. Epub 2010 Oct 17.
8	Studies on the different modes of action of the anticoagulant protease inhibitors DX-9065a and Argatroban. I. Effects on thrombin generation. J Biol Chem. 2002 Dec 27;277(52):50439-44.
9	New antithrombotic drugs (excluding plasminogen activators. Arch Mal Coeur Vaiss. 2001 Nov;94(11 Suppl):1225-32.
10	New anticoagulants. Am Heart J. 2001 Aug;142(2 Suppl):S3-8.
11	Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
12	Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
13	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14	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. (Target id: 2362).
15	Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis. Kidney Int Suppl. 1999 Nov;(72):S46-50.
16	Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption. Pharmacotherapy. 2003 Apr;23(4):533-6.
17	Antithrombin III Utilization in a Large Teaching Hospital. P T. 2013 December; 38(12): 764-767, 779.
18	SMPDB database: Vitamin K Metabolism
19	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
20	Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
21	Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
22	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
23	The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
24	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
25	Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
26	Effects of rosiglitazone and atorvastatin on the expression of genes that control cholesterol homeostasis in differentiating monocytes. Biochem Pharmacol. 2006 Feb 28;71(5):605-14.
27	Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin. Pharmacol Res. 2007 Apr;55(4):310-7. doi: 10.1016/j.phrs.2006.12.009. Epub 2007 Jan 14.
28	Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
29	Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
30	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
31	Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
32	Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
33	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
34	CYP4F2 genetic variant alters required warfarin dose. Blood. 2008 Apr 15;111(8):4106-12. doi: 10.1182/blood-2007-11-122010. Epub 2008 Feb 4.
35	Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
36	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
37	Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
38	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
39	CYP4F2 repression and a modified alpha-tocopherol (vitamin E) metabolism are two independent consequences of ethanol toxicity in human hepatocytes. Toxicol In Vitro. 2017 Apr;40:124-133.
40	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.