warfarin [cytosol]

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The anticoagulant drug warfarin inhibits VKORC1 (Whitlon et al. 1978), thereby reducing clotting ability (Choonara et al. 1985, 1988), which is used as a treatment for thrombotic disorders such as deep vein thrombosis (DVT), pulmonary embolism and to prevent stroke (Ageno et al. 2012). A common side-effect of warfarin anticoagulation is bleeding which can be counteracted by vitamin K supplementation (Ageno et al. 2012). The exact mechanism by which warfarin inhibits VKORC1 remains elusive. Several recent mechanistic studies suggest competitive binding of a key residue in VKORC1 (Czogalla et al. 2017) or blockage of a dynamic electron-transfer process in VKORC1 (Shen et al. 2017).

Literature References
PubMed ID Title Journal Year
22315269 Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Ageno, W, Gallus, AS, Hylek, EM, Crowther, M, Wittkowsky, A, Palareti, G

Chest 2012
27918545 Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer

Gross, ML, Liu, Q, Li, S, Zhou, F, Cui, W, Li, W, Bowman, GR, Sadler, JE, Huang, W, Shen, G, Yang, Y, Zhang, H

Nat. Struct. Mol. Biol. 2017
4091996 Vitamin K1 metabolism in relation to pharmacodynamic response in anticoagulated patients

Choonara, IA, Haynes, BP, Breckenridge, AM, Cholerton, S, Scott, AK, Park, BK

Br J Clin Pharmacol 1985
27941861 Warfarin and vitamin K compete for binding to Phe55 in human VKOR

Biswas, A, Oldenburg, J, Watzka, M, Liphardt, K, Hornung, V, Höning, K, Czogalla, KJ

Nat. Struct. Mol. Biol. 2017
3370190 The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin

Preston, FE, Hay, CR, Choonara, IA, Haynes, BP, Breckenridge, AM, Malia, RG, Cholerton, S, Park, BK

Br J Clin Pharmacol 1988
23919835 Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon

Maitland-van der Zee, AH, de Boer, A, van Schie, RM, Daly, AK, Redekop, WK, Verhoef, TI

Br J Clin Pharmacol 2014
646989 Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition

Whitlon, DS, Sadowski, JA, Suttie, JW

Biochemistry 1978
25639072 [On the history of vitamin K, dicoumarol and warfarin]

Permin, H, Kruse, PR, Norn, S, Kruse, E

Dan Medicinhist Arbog 2014
External Reference Information
Name Identifier Synonyms
pulmonary embolism DOID:9477 pulmonary embolus, pulmonary artery embolism
Cross References
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