Identification of novel small molecule inhibitors of activated protein C

Thrombosis Research

Volumn 133, Issue 6, 2014, Pages 1105-1114

  Sperandio, Olivier ^a   Wildhagen, Karin C A A ^b   Schrijver, Roy ^b   Wielders, Simone ^b   Villoutreix, Bruno O ^a   Nicolaes, Gerry A F ^b  

^a INSERM   (France)

^b MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

Activated protein C; Drug design; Factor Va; Virtual screening

Indexed keywords

ACTIVATED PROTEIN C; BLOOD CLOTTING FACTOR 5; BLOOD CLOTTING FACTOR 8; PLASMINOGEN ACTIVATOR INHIBITOR 3; THROMBIN; MOLECULAR LIBRARY; PROTEIN C;

ARTICLE; BINDING AFFINITY; BINDING SITE; COMPUTER MODEL; CONTROLLED STUDY; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN CLEAVAGE; PROTEIN PROTEIN INTERACTION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG SCREENING; METABOLISM; MOLECULAR LIBRARY; PHARMACOLOGY; PROCEDURES; STRUCTURE ACTIVITY RELATION; SURFACE PLASMON RESONANCE;

BINDING SITES; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; MODELS, MOLECULAR; PROTEIN C; PROTEIN C INHIBITOR; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; SURFACE PLASMON RESONANCE;

EID: 84900503009     PISSN: 00493848     EISSN: 18792472     Source Type: Journal    
DOI: 10.1016/j.thromres.2014.01.026     Document Type: Article

References (49)

1. K.C. Wildhagen, E. Lutgens, S.T. Loubele, H. ten Cate, and G.A. Nicolaes The structure-function relationship of activated protein C. Lessons from natural and engineered mutations Thromb Haemost 106 2011 1034 1045
2. R.A. Marlar, and A. Neumann Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies Semin Thromb Hemost 16 1990 299 309
3. G.A.F. Nicolaes, and B. Dahlback Congenital and acquired activated protein C resistance Semin Vasc Med 3 2003 33 46
4. J.H. Griffin, J.A. Fernandez, A.J. Gale, and L.O. Mosnier Activated protein C J Thromb Haemost 5 Suppl. 1 2007 73 80
5. F. Espana, I. Zuazu, V. Vicente, A. Estelles, P. Marco, and J. Aznar Quantification of circulating activated protein C in human plasma by immunoassays-enzyme levels are proportional to total protein C levels Thromb Haemost 75 1996 56 61
6. T. Mather, V. Oganessyan, P. Hof, R. Huber, S. Foundling, and C. Esmon et al. The 2.8 A crystal structure of Gla-domainless activated protein C EMBO J 15 1996 6822 6831
7. G.A.F. Nicolaes, G. Tans, M.C. Thomassen, H.C. Hemker, I. Pabinger, and K. Varadi et al. Peptide bond cleavages and loss of functional activity during inactivation of factor Va and factor VaR506Q by activated protein C J Biol Chem 270 1995 21158 21166
8. D. Lu, M. Kalafatis, K.G. Mann, and G.L. Long Comparison of activated protein C/protein S-mediated inactivation of human factor VIII and factor V Blood 87 1996 4708 4717
9. L.O. Mosnier, B.V. Zlokovic, and J.H. Griffin The cytoprotective protein C pathway Blood 109 2007 3161 3172
10. J.H. Griffin, B.V. Zlokovic, and L.O. Mosnier Protein C anticoagulant and cytoprotective pathways Int J Hematol 95 2012 333 345
11. B. Dahlback, M. Carlsson, and P.J. Svensson Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C Proc Natl Acad Sci U S A 90 1993 1004 1008
12. R.M. Bertina, B.P. Koeleman, T. Koster, F.R. Rosendaal, R.J. Dirven, and H. de Ronde et al. Mutation in blood coagulation factor V associated with resistance to activated protein C Nature 369 1994 64 67
13. B. Dahlback, and B. Hildebrand Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V Proc Natl Acad Sci U S A 91 1994 1396 1400
14. L. Shen, and B. Dahlback Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor VIIIa J Biol Chem 269 1994 18735 18738
15. M.H. Bos, D.W. Meijerman, C. van der Zwaan, and K. Mertens Does activated protein C-resistant factor V contribute to thrombin generation in hemophilic plasma? J Thromb Haemost 3 2005 522 530
16. S. Butenas, T. Orfeo, M. Kalafatis, and K.G. Mann Peptidomimetic inhibitors for activated protein C: implications for hemophilia management J Thromb Haemost 4 2006 2411 2416
17. D.H. Lee, I.R. Walker, J. Teitel, M.C. Poon, B. Ritchie, and J. Akabutu et al. Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A Thromb Haemost 83 2000 387 391
18. W.C. Nichols, K. Amano, P.M. Cacheris, M.S. Figueiredo, K. Michaelides, and R. Schwaab et al. Moderation of hemophilia A phenotype by the factor V R506Q mutation Blood 88 1996 1183 1187
19. A. Schlachterman, J. Schuettrumpf, J.H. Liu, C. Furlan Freguia, R. Toso, and M. Poncz et al. Factor V Leiden improves in vivo hemostasis in murine hemophilia models J Thromb Haemost 3 2005 2730 2737
20. C. van 't Veer, N.J. Golden, M. Kalafatis, P. Simioni, R.M. Bertina, and K.G. Mann An in vitro analysis of the combination of hemophilia A and factor V(LEIDEN) Blood 90 1997 3067 3072
21. G. De Nanteuil, P. Gloanec, S. Beguin, P.L. Giesen, H.C. Hemker, and P. Mennecier et al. Low molecular weight activated protein C inhibitors as a potential treatment for hemophilic disorders J Med Chem 49 2006 5047 5050
22. G.A.F. Nicolaes, B.O. Villoutreix, and B. Dahlback Partial glycosylation of Asn2181 in human factor V as a cause of molecular and functional heterogeneity. Modulation of glycosylation efficiency by mutagenesis of the consensus sequence for N-linked glycosylation Biochemistry 38 1999 13584 13591
23. J. Rosing, G. Tans, J.W. Govers-Riemslag, R.F. Zwaal, and H.C. Hemker The role of phospholipids and factor Va in the prothrombinase complex J Biol Chem 255 1980 274 283
24. U. Friedrich, B. Potzsch, K.T. Preissner, G. Muller-Berghaus, and H. Ehrlich Calcium-dependent activation of protein C by thrombin/thrombomudulin: role of negatively charged amino acids within the activation peptide of protein C Thromb Haemost 72 1994 567 572
25. Y.H. Sun, L. Shen, and B. Dahlback Gla domain-mutated human protein C exhibiting enhanced anticoagulant activity and increased phospholipid binding Blood 101 2003 2277 2284
26. J.H. Griffin, B. Evatt, T.S. Zimmerman, A.J. Kleiss, and C. Wideman Deficiency of protein C in congenital thrombotic disease J Clin Invest 68 1981 1370 1373
27. G.A.F. Nicolaes, P.E. Bock, K. Segers, K.C. Wildhagen, B. Dahlback, and J. Rosing Inhibition of thrombin formation by active site mutated (S360A) activated protein C J Biol Chem 285 2010 22890 22900
28. A. Volkamer, D. Kuhn, F. Rippmann, and M. Rarey DoGSiteScorer: a web server for automatic binding site prediction, analysis and druggability assessment Bioinformatics. 28 2012 2074 2075
29. C.H. Ngan, D.R. Hall, B. Zerbe, L.E. Grove, D. Kozakov, and S. Vajda FTSite: high accuracy detection of ligand binding sites on unbound protein structures Bioinformatics 28 2012 286 287
30. B. Huang MetaPocket: a meta approach to improve protein ligand binding site prediction OMICS 13 2009 325 330
31. T.B. Leite, D. Gomes, M.A. Miteva, J. Chomilier, B.O. Villoutreix, and P. Tuffery Frog: a FRee Online druG 3D conformation generator Nucleic Acids Res 35 2007 W568 W572
32. A.N. Jain Surflex-Dock 2.1: robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search J Comput Aided Mol Des 21 2007 281 306
33. G.A.F. Nicolaes, M.C. Thomassen, R. van Oerle, K. Hamulyak, H.C. Hemker, and G. Tans et al. A prothrombinase-based assay for detection of resistance to activated protein C Thromb Haemost 76 1996 404 410
34. K. Segers, B. Dahlback, J. Rosing, and G.A.F. Nicolaes Identification of surface epitopes of human coagulation factor Va that are important for interaction with activated protein C and heparin J Biol Chem 283 2008 22573 22581
35. A.J. Gale, M.J. Heeb, and J.H. Griffin The autolysis loop of activated protein C interacts with factor Va and differentiates between the Arg506 and Arg306 cleavage sites Blood 96 2000 585 593
36. U. Friedrich, G.A.F. Nicolaes, B.O. Villoutreix, and B. Dahlback Secondary substrate-binding exosite in the serine protease domain of activated protein C important for cleavage at Arg-506 but not at Arg-306 in factor Va J Biol Chem 276 2001 23105 23108
37. A.J. Gale, A. Tsavaler, and J.H. Griffin Molecular characterization of an extended binding site for coagulation factor Va in the positive exosite of activated protein C J Biol Chem 277 2002 28836 28840
38. G.A.F. Nicolaes, K.W. Sorensen, U. Friedrich, G. Tans, J. Rosing, and L. Autin et al. Altered inactivation pathway of factor Va by activated protein C in the presence of heparin Eur J Biochem 271 2004 2724 2736
39. M. Takeyama, J.M. Wintermute, C. Manithody, A.R. Rezaie, and P.J. Fay Variable contributions of basic residues forming an APC exosite in the binding and inactivation of factor VIIIa Biochemistry 52 2013 2228 2235
40. T.J. Cramer, and A.J. Gale Function of the activated protein C (APC) autolysis loop in activated FVIII inactivation Br J Haematol 153 2011 644 654
41. H.C. Hemker, R. Al Dieri, E. De Smedt, and S. Beguin Thrombin generation, a function test of the haemostatic-thrombotic system Thromb Haemost 96 2006 553 561
42. K. Padmanabhan, K.P. Padmanabhan, J.D. Ferrara, J.E. Sadler, and A. Tulinsky The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer J Biol Chem 268 1993 17651 17654
43. C.A. Holland, A.T. Henry, H.C. Whinna, and F.C. Church Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin FEBS Lett 484 2000 87 91
44. M.T. Murakami, J. Rios-Steiner, S.E. Weaver, A. Tulinsky, J.H. Geiger, and R.K. Arni Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum J Mol Biol 366 2007 602 610
45. M.S. Dennis, C. Eigenbrot, N.J. Skelton, M.H. Ultsch, L. Santell, and M.A. Dwyer et al. Peptide exosite inhibitors of factor VIIa as anticoagulants Nature 404 2000 465 470
46. K. Carlsson, E. Persson, U. Carlsson, and M. Svensson Inhibitors of factor VIIa affect the interface between the protease domain and tissue factor Biochem Biophys Res Commun 349 2006 1111 1116
47. J. Muller, B. Isermann, C. Ducker, M. Salehi, M. Meyer, and M. Friedrich et al. An exosite-specific ssDNA aptamer inhibits the anticoagulant functions of activated protein C and enhances inhibition by protein C inhibitor Chem Biol 16 2009 442 451
48. L. Yang, C. Manithody, and A.R. Rezaie Contribution of basic residues of the 70-80-loop to heparin binding and anticoagulant function of activated protein C Biochemistry 41 2002 6149 6157
49. S.W. Gal, S. Amontov, P.T. Urvil, D. Vishnuvardhan, F. Nishikawa, and P.K. Kumar et al. Selection of a RNA aptamer that binds to human activated protein C and inhibits its protease function Eur J Biochem 252 1998 553 562