Novel Small Molecule Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa) from Natural Product Anabaenopeptin

Journal of Medicinal Chemistry

Volumn 58, Issue 11, 2015, Pages 4839-4844

  Halland, Nis ^a   Brönstrup, Mark ^b   Czech, Jörg ^a   Czechtizky, Werngard ^a   Evers, Andreas ^a   Follmann, Markus ^c   Kohlmann, Markus ^a   Schiell, Matthias ^a   Kurz, Michael ^a   Schreuder, Herman A ^a   Kallus, Christopher ^a  

^a Sanofi R and D   (Germany)

^b Centre for Infection Research   (Germany)

^c BAYER PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 [[1 TERT BUTOXYCARBONYL 5 (TERT BUTOXYCARBONYLAMINO)PENTYL]CARBAMOYLAMINO] 3 CYCLOHEXYLPROPANOIC ACID; 6 AMINO 2 [[2(CYCLOHEXYLAMINO) 1 (CYCLOHEXYLMETHYL) 2 OXO ETHYL]CARBAMOYLAMINO]HEXANOIC ACID; ANABAENOPEPTIN; CARBOXYPEPTIDASE B; NATURAL PRODUCT; PEPTIDE HYDROLASE INHIBITOR; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR; UNCLASSIFIED DRUG; BIOLOGICAL PRODUCT; CYCLOPEPTIDE; MOLECULAR LIBRARY;

ARTICLE; BACTERIUM ISOLATION; CYANOBACTERIUM; DRUG DESIGN; DRUG IDENTIFICATION; DRUG PROTEIN BINDING; IN VITRO STUDY; NONHUMAN; PHYSICAL CHEMISTRY; PORCINE MODEL; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; FIBRINOLYSIS; HUMAN; MICROSOME; MOLECULAR LIBRARY; MOUSE; PHARMACOLOGY; PIG; RAT; X RAY CRYSTALLOGRAPHY;

ANIMALS; BIOLOGICAL PRODUCTS; CARBOXYPEPTIDASE B2; CELLS, CULTURED; CRYSTALLOGRAPHY, X-RAY; CYANOBACTERIA; FIBRINOLYSIS; HUMANS; MICE; MICROSOMES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PEPTIDES, CYCLIC; RATS; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; SWINE;

EID: 84931282063     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm501840b     Document Type: Article

References (34)

1. Gresele, P.; Agnelli, G. Novel approaches to the treatment of thrombosis Trends Pharmacol. Sci. 2002, 23, 25-32
2. Bajzar, L.; Manuel, R.; Nesheim, M. E. Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor J. Biol. Chem. 1995, 270, 14477-14484
3. Bouma, B. N.; Meijers, J. C. M. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U) J. Thromb. Haemostasis 2003, 1, 1566-1574
4. Vercauteren, E.; Gils, A.; Declerck, P. J. Thrombin activatable fibrinolysis inhibitor: a putative target to enhance fibrinolysis Semin. Thromb. Hemostasis 2013, 4, 365-372
5. Fernandez, D.; Pallares, I.; Covaleda, G.; Aviles, F. X.; Vendrell, J. Metallocarboxypeptidases and their inhibitors: recent developments in biomedically relevant protein and organic ligands Curr. Med. Chem. 2013, 20, 1595-1608
6. Willemse, J. L.; Heylen, E.; Nesheim, M. E.; Hendriks, D. F. Carboxypeptidase U (TAFIa): a new drug target for fibrinolytic therapy? J. Thromb. Haemostasis 2009, 7, 1962-1971
7. Vercauteren, E.; Peeters, M.; Hoylaerts, M. F.; Lijnen, H. R.; Meijers, J. C. M.; Declerck, P. J.; Gils, A. The hyperfibrinolytic state of mice with combined thrombin-activatable fibrinolysis (TAFI) and plasminogen activator inhibitor-1 gene deficiency is critically dependent on TAFI deficiency J. Thromb. Haemostasis 2012, 10, 2555-2562
8. Hendriks, D.; Scharpé, S.; van. Sande, M.; Lommaert, M. P. Characterisation of a carboxypeptidase in human serum distinct from carboxypeptidase N J. Clin. Chem. Clin. Biochem. 1989, 27, 277-285
9. Campbell, W.; Okada, H. An arginine specific carboxypeptidase generated in blood during coagulation or inflammation which is unrelated to carboxypeptidase N or its subunits Biochem. Biophys. Res. Commun. 1989, 162, 933-939
10. Tan, A. K.; Eaton, D. L. Activation and characterization of procarboxypeptidase B from human plasma Biochemistry 1995, 34, 5811-5816
11. Christianson, D. W.; Lipscomb, W. N. Carboxypeptidase A Acc. Chem. Res. 1989, 22, 62-69
12. Vendrell, J.; Querol, E.; Avilés, F. X. Metallocarboxypeptidases and their protein inhibitors. Structure, function and biomedical properties Biochim. Biophys. Acta 2000, 1477, 284-298
13. Jensen, A. F.; Burkrinsky, J. T.; Bjerrum, M. J.; Larsen, S. Three high-resolution crystal structures of cadmium-substituted carboxypeptidase A provide insights into enzymatic function J. Biol. Inorg. Chem. 2002, 7, 490-499
14. Wang, Y.-X.; Zhao, L.; Nagashima, M.; Vincelette, J.; Sukovich, D.; Li, W.; Subramanyam, B.; Yuan, S.; Emayan, K.; Islam, I.; Hrvatin, P.; Bryant, J.; Light, D. R.; Vergona, R.; Morser, J.; Buckman, B. O. A novel inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa)-Part I: Pharmacological characterization J. Thromb. Haemostasis 2007, 97, 45-53
15. Wang, Y.-X.; da Cunha, V.; Vincelette, J.; Zhao, L.; Nagashima, M.; Kawai, K.; Yuan, S.; Emayan, K.; Islam, I.; Hosoya, J.; Sullivan, M. E.; Dole, W. P.; Morser, J.; Buckman, B. O.; Vergona, R. A novel inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa)-Part II: Enhancement of both exogenous and endogenous fibrinolysis in animal models of thrombosis J. Thromb. Haemostasis 2007, 97, 54-61
16. Polla, M. Chemical compounds. WO 003027128, 2003.
17. Brink, M.; Dahlen, A.; Olsson, T.; Polla, M.; Svensson, T. Design and synthesis of conformationally restricted inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa) Bioorg. Med. Chem. 2014, 22, 2261-2268
18. Linschoten, M.; Polla, M.; Svenson, P. New compounds. WO2000066557, 2000.
19. For general zinc bonding properties of hydroxamic acids, see Chen, K.; Xu, L.; Wiest, O. Computational exploration of zinc binding groups for HDAC inhibition J. Org. Chem. 2013, 78, 5051-5055
20. Doo, Y. H.; Gifford-Moore, D. S.; Beight, D. W.; Rathnachalam, R.; Klimkowski, V. J.; Warshawsky, A. M.; Li, D. Inhibition of thrombin activatable fibrinolysis inhibitor by cysteine derivatives Thromb. Res. 2005, 116, 265-271
21. Polla, M. O.; Tottie, L.; Norden, C.; Linschoten, M.; Müsil, D.; Trumpp-Kallmeyer, S.; Aukrust, I. R.; Ringom, R.; Holm, K. H.; Neset, S. M.; Sandberg, M.; Thurmond, J.; Yu, P.; Hategan, G.; Anderson, H. Design and synthesis of potent orally active, inhibitors, inhibitors of carboxypeptidase U (TAFIa) Bioorg. Med. Chem. 2004, 12, 1151-1175
22. Barrow, J. C.; Nantermet, P. G.; Stauffer, S. R.; Ngo, P. L.; Steinbeiser, M. A.; Mao, S.-S.; Carroll, S. S.; Balley, C.; Colussi, D.; Bosserman, M.; Burlein, C.; Cook, J. J.; Sitko, G.; Tiller, P. R.; Miller-Stein, C. M.; Rose, M.; McMasters, D. R.; Vacca, J. P.; Selnick, H. G. Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics J. Med. Chem. 2003, 46, 5294-5297
23. Hendrickx, M. L. V.; Zatloukalova, M.; Hassanzadeh-Ghassabeh, G.; Muyldermans, S.; Gils, A.; Declerck, P. J. Identification of a novel, nanobody induced, mechanism of TAFI inactivation and its in vivo application J. Thromb. Haemostasis 2014, 12, 229-236
24. Semeraro, F.; Ammollo, C. T.; Gils, A.; Declerck, P. J.; Coluccci, M. Monoclonal antibodies targeting the antifibrinolytic activity of activated thrombin-activatable fibrinolysis inhibitor but not the anti-inflammatory activity on osteopontin and C5a J. Thromb. Haemostasis 2013, 11, 2137-2147
25. Kallus, C.; Broenstrup, M.; Czechtizky, W.; Evers, A.; Follmann, M.; Halland, N.; Schreuder, H. Urea and sulfamide derivatives as tafia inhibitors. WO 2008067909, 2008.
26. Kalaitzis, J. A.; Lauro, F. M.; Neilan, B. A. Mining cyanobacterial genomes for genes encoding complex biosynthetic pathways Nat. Prod. Rep. 2009, 26, 1447-1465
27. Niedermayer, T.; Broenstrup, M. Natural Product Drug Discovery from Microalgae, Microalgal Biotechnology; Posten, C.; Walter, C., Eds.; Walter de Gruyter: Berlin, 2012; pp 169-202.
28. Leão, P. N.; Engene, N.; Antunes, A.; Gerwick, W. H.; Vasconcelosac, V. The chemical ecology of cyanobacteria Nat. Prod. Rep. 2012, 29, 372-391
29. Murakami, M.; Suzuki, S.; Itou, Y.; Kodani, S.; Ishida, K. New anabaenopeptins, potent carboxypeptidase-A inhibitors from the cyanobacterium aphanizomenon flos-aquae J. Nat. Prod. 2000, 63, 1280-1282
30. Itou, Y.; Suzuki, S.; Ishida, K.; Murakami, M. Anabaenopeptins G and H, potent carboxypeptidase A inhibitors from the cyanobacterium Oscillatoria agardhii (NIES-595) Bioorg. Med. Chem. Lett. 1999, 9, 1243-1246
31. Björquist, P.; Buchanan, M.; Campitelli, M.; Carroll, A.; Hyde, E.; Neve, J.; Polla, M.; Quinn, R. Use of cyclic anabaenopeptin-type peptides for the treatment of a condition wherein inhibition of carboxypeptidase u is beneficial, novel anabaenopeptin derivatives and intermediates thereof. WO2005039617, 2005.
32. Boffa, M. B.; Wang, W.; Bajzar, L.; Nesheim, M. E. Plasma and recombinant thrombin-activatable fibrinolysis inhibitor (TAFI) and activated TAFI compared with respect to glycosylation, thrombin/thrombomodulin-dependent activation, thermal stability, and enzymatic properties J. Biol. Chem. 1998, 273, 2127-2135
33. Marx, P. F.; Harma, T.; Brondijk, C.; Plug, T.; Romijn, R. A.; Hemrika, W.; Meijers, J. C. M.; Huizinga, E. G. Crystal structure of TAFI elucidate the inactivation mechanism of activated TAFI: a novel mechanism for enzyme autoregulation Blood 2008, 112, 2803-2809
34. Anand, K.; Pallares, I.; Valnickova, Z.; Christensen, T.; Vendrell, J.; Wendt, K. U.; Schreuder, H. A.; Enghild, J. J.; Avilés, F. X. The crystal structure of thrombin-activatable fibrinolysis inhibitor (TAFI) provides the structural basis for its intrinsic activity and the short half-life of TAFIa J. Biol. Chem. 2008, 283, 29416-29423