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Pathway Description
Dicoumarol Action Pathway
Homo sapiens
Drug Action Pathway
Dicoumarol (also known as bishydroxycoumarin) is an anticoagulant that inhibit the liver enzyme vitamin K reductase, which cause Vitamin K1 2,3-epoxide could not be catalyzed by vitamin K reductase to form vitamin KH2, the reduced form of vitamin K. Vitamin K-dependent coagulation factors (II, VII, IX, and X) requires its cofactor, vitamin K to facilitate the activation and gamma-carboxylation. Inhibition of vitamin K reductase results in reduced concentration of vitamin KH2, which will ultimately lead to decreased coagulability of the blood and reduced cleavage of fibrinogen into fibrin.
References
Dicoumarol Pathway References
Cullen JJ, Hinkhouse MM, Grady M, Gaut AW, Liu J, Zhang YP, Weydert CJ, Domann FE, Oberley LW: Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. Cancer Res. 2003 Sep 1;63(17):5513-20.
Pubmed: 14500388
Mironov AA, Colanzi A, Polishchuk RS, Beznoussenko GV, Mironov AA Jr, Fusella A, Di Tullio G, Silletta MG, Corda D, De Matteis MA, Luini A: Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport. Eur J Cell Biol. 2004 Jul;83(6):263-79. doi: 10.1078/0171-9335-00377.
Pubmed: 15511084
Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz LO: Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication. Arch Biochem Biophys. 2005 Feb 15;434(2):241-7. doi: 10.1016/j.abb.2004.11.002.
Pubmed: 15639223
Thanos CG, Liu Z, Reineke J, Edwards E, Mathiowitz E: Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride. Pharm Res. 2003 Jul;20(7):1093-100.
Pubmed: 12880296
Coagulation References
van der Meijden PE, Munnix IC, Auger JM, Govers-Riemslag JW, Cosemans JM, Kuijpers MJ, Spronk HM, Watson SP, Renne T, Heemskerk JW: Dual role of collagen in factor XII-dependent thrombus formation. Blood. 2009 Jul 23;114(4):881-90. doi: 10.1182/blood-2008-07-171066. Epub 2009 Apr 16.
Pubmed: 19372258
Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83.
Pubmed: 12787532
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