Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEUC8H)

• DTT Name: Vitamin K epoxide reductase complex 1 (VKORC1)
• Synonyms: Vitamin K1 2,3-epoxide reductase subunit 1; VKORC1; VKOR; UNQ308/PRO351; MSTP576; MSTP134
• Gene Name: VKORC1
• DTT Type: Successful target; [1]
• Related Disease:
  Bleeding disorder [ICD-11: GA20-GA21]
  Coagulation defect [ICD-11: 3B10]
  Pulmonary thromboembolism [ICD-11: BB00]
  Supraventricular tachyarrhythmia [ICD-11: BC81]
  Thrombosis [ICD-11: DB61-GB90]
• BioChemical Class: Short-chain dehydrogenases reductase
• UniProt ID: VKOR1_HUMAN
• TTD ID: T11843
• EC Number: EC 1.17.4.4
• Sequence:
  MGSTWGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWG
  RGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSVYL
  AWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH
• Function: Involved invitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.
• Reactome Pathway: Metabolism of vitamin K (R-HSA-6806664)
• BioCyc Pathway: MetaCyc:HS15548-MON

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acenocoumarol	DMH75KV	Thrombosis	DB61-GB90	Approved	[2], [3], [4]
Dicumarol	DMFQCB1	Bleeding disorder	GA20-GA21	Approved	[1]
Phenindione	DM2PYNR	Coagulation defect	3B10.0	Approved	[4]
Phenprocoumon	DMDO279	Thrombosis	DB61-GB90	Approved	[4]
Warfarin	DMJYCVW	Atrial fibrillation	BC81.3	Approved	[4]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tecarfarin	DMTCR2O	Cerebrovascular ischaemia	8B1Z	Phase 3	[5]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Vitamin K1 2,3-epoxide reductase 1 (VKOR) DME Info
• Gene Name: VKORC1

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Menadiol sodium diphosphate	DMP9N85	Coagulation defect	3B10.0	Approved	[6]

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin K	DMN6EZY	Discovery agent	N.A.	Investigative	[7]

References

• [1] Vitamin K antagonism of coumarin intoxication in the rat. Thromb Haemost. 1986 Apr 30;55(2):235-9.
• [2] Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity. Mol Biol Rep. 2010 Apr;37(4):1693-7.
• [3] Genotypes associated with reduced activity of VKORC1 and CYP2C9 and their modification of acenocoumarol anticoagulation during the initial treatmen... Clin Pharmacol Ther. 2009 Apr;85(4):379-86.
• [4] [Oral anticoagulation and pharmacogenetics: importance in the clinical setting]. Rev Med Suisse. 2007 Sep 12;3(124):2030, 2033-4, 2036.
• [5] Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants. J Clin Pharmacol. 2011Apr;51(4):561-74.
• [6] SMPDB database: Vitamin K Metabolism
• [7] VKORC1L1, an enzyme mediating the effect of vitamin K in liver and extrahepatic tissues. Nutrients. 2018 Jul 26;10(8). pii: E970.