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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Chemical Compound Review

SureCN1649552     2-[[2-[[3- (diaminomethylidene)-6-oxo- 1...

Synonyms: FT-0668536, AC1O5FK6
 
 
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Disease relevance of ZK 807834

 

High impact information on ZK 807834

  • The crystal structure of the complex shows that the amidine of ZK-807834 forms a salt bridge with Asp189 in the S1 pocket and the basic imidazoline fits snugly into the S4 site [4].
  • Discovery of N-[2-[5-[Amino(imino)methyl]-2-hydroxyphenoxy]-3, 5-difluoro-6-[3-(4, 5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylgl y cine (ZK-807834): a potent, selective, and orally active inhibitor of the blood coagulation enzyme factor Xa [5].
  • This study was designed to determine whether a novel, synthetic inhibitor of FXa (ZK-807834, molecular mass 527 Da, K(i) = 0.11 nM) administered during and briefly after pharmacologic coronary fibrinolysis increases 24-h patency [6].
  • Studies in animals have shown that ZK-807834 attenuates thrombosis and thrombus progression after fibrinolysis and exhibits an increased antithrombotic-to-bleeding risk ratio compared with conventional agents [7].
  • Human in vitro pharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (CI-1031) [7].
 

Biological context of ZK 807834

 

Gene context of ZK 807834

 

Analytical, diagnostic and therapeutic context of ZK 807834

  • This paper presents the structure of the inhibitor ZK-807834, also known as CI-1031, bound to factor Xa and provides the details of the protein purification and crystallization [4].

References

  1. The antithrombotic effects of CI-1031 (ZK-807834) and enoxaparin in a canine electrolytic injury model of arterial and venous thrombosis. McClanahan, T.B., Hicks, G.W., Morrison, A.L., Peng, Y.W., Janiczek-Dolphin, N., Mertz, T.E., Sullivan, M.E., Morser, J., Juneau, P.L., Leadley, R. Eur. J. Pharmacol. (2001) [Pubmed]
  2. Assessment of ex vivo pharmacodynamic markers during inhibition of thrombosis by CI-1031 (ZK-807834), a novel direct factor Xa inhibitor. Chi, L., Pen, Y.W., Potoczak, R., Gibson, G., Hicks, G., Mertz, T.E., Janiczek, N., Juneau, P.L., Gallagher, K., Leadley, R. Pharmacology (2002) [Pubmed]
  3. FXa-induced responses in vascular wall cells are PAR-mediated and inhibited by ZK-807834. McLean, K., Schirm, S., Johns, A., Morser, J., Light, D.R. Thromb. Res. (2001) [Pubmed]
  4. Preparation, characterization, and the crystal structure of the inhibitor ZK-807834 (CI-1031) complexed with factor Xa. Adler, M., Davey, D.D., Phillips, G.B., Kim, S.H., Jancarik, J., Rumennik, G., Light, D.R., Whitlow, M. Biochemistry (2000) [Pubmed]
  5. Discovery of N-[2-[5-[Amino(imino)methyl]-2-hydroxyphenoxy]-3, 5-difluoro-6-[3-(4, 5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylgl y cine (ZK-807834): a potent, selective, and orally active inhibitor of the blood coagulation enzyme factor Xa. Phillips, G.B., Buckman, B.O., Davey, D.D., Eagen, K.A., Guilford, W.J., Hinchman, J., Ho, E., Koovakkat, S., Liang, A., Light, D.R., Mohan, R., Ng, H.P., Post, J.M., Shaw, K.J., Smith, D., Subramanyam, B., Sullivan, M.E., Trinh, L., Vergona, R., Walters, J., White, K., Whitlow, M., Wu, S., Xu, W., Morrissey, M.M. J. Med. Chem. (1998) [Pubmed]
  6. A novel synthetic inhibitor of factor Xa decreases early reocclusion and improves 24-h patency after coronary fibrinolysis in dogs. Abendschein, D.R., Baum, P.K., Verhallen, P., Eisenberg, P.R., Sullivan, M.E., Light, D.R. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  7. Human in vitro pharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (CI-1031). Post, J.M., Sullivan, M.E., Abendschein, D., Ewing, J., Hinchman, J.W., Light, D.R. Thromb. Res. (2002) [Pubmed]
  8. Effects of ZK-807834, a novel inhibitor of factor Xa, on arterial and venous thrombosis in rabbits. Abendschein, D.R., Baum, P.K., Martin, D.J., Vergona, R., Post, J., Rumennik, G., Sullivan, M.E., Eisenberg, P.R., Light, D.R. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
 
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