Discovery of novel allosteric non-bisphosphonate inhibitors of farnesyl pyrophosphate synthase by integrated lead finding

ChemMedChem

Volumn 10, Issue 11, 2015, Pages 1884-1891

  Marzinzik, Andreas L ^a   Amstutz, René ^a,b   Bold, Guido ^a   Bourgier, Emmanuelle ^a   Cotesta, Simona ^a   Glickman, J Fraser ^a,c   Götte, Marjo ^a   Henry, Christelle ^a   Lehmann, Sylvie ^a   Hartwieg, J Constanze D ^a   Ofner, Silvio ^a   Pellé, Xavier ^a   Roddy, Thomas P ^a,d   Rondeau, Jean Michel ^a   Stauffer, Frédéric ^a   Stout, Steven J ^a,e   Widmer, Armin ^a   Zimmermann, Johann ^a,f   Zoller, Thomas ^a   Jahnke, Wolfgang ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b Conim AG ^*  (Switzerland)

^c ROCKEFELLER UNIVERSITY   (United States)

^d Agios   (United States)

^e MERCK RESEARCH LABORATORIES   (United States)

^f Polyphor Ltd   (Switzerland)

Author keywords

allosteric inhibitors; anti infective drug discovery; antitumor agents; FPPS; immunomodulation; immunotherapy

Indexed keywords

AGENTS AFFECTING METABOLISM; FARNESYL PYROPHOSPHATE SYNTHASE INHIBITOR; QUINOLINE DERIVATIVE; SALICYLIC ACID DERIVATIVE; TRANSFERASE INHIBITOR; UNCLASSIFIED DRUG; ENZYME INHIBITOR; GERANYLTRANSFERASE; QUINOLINE; SALICYLIC ACID;

ALLOSTERISM; ARTICLE; BONE MINERAL; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG STRUCTURE; DRUG SYNTHESIS; ESTERIFICATION; IC50; IN VITRO STUDY; ISOTHERMAL TITRATION CALORIMETRY; PRIORITY JOURNAL; STATIC ELECTRICITY; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG DEVELOPMENT; DRUG EFFECTS; HUMAN; METABOLISM; SYNTHESIS;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; ENZYME INHIBITORS; GERANYLTRANSTRANSFERASE; HUMANS; MOLECULAR STRUCTURE; QUINOLINES; SALICYLIC ACID; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84946494366     PISSN: 18607179     EISSN: 18607187     Source Type: Journal    
DOI: 10.1002/cmdc.201500338     Document Type: Article

References (39)

1. A. S. Kesselheim, J. Avorn, Nat. Rev. Drug Discovery 2013, 12, 425-443.
2. R. G. G. Russell, N. B. Watts, F. H. Ebetino, M. J. Rogers, Osteoporosis Int. 2008, 19, 733-759.
3. M. J. Rogers, J. C. Crockett, F. P. Coxon, J. Monkkonen, Bone 2011, 49, 34-41.
4. F. P. Coxon, K. Thompson, M. J. Rogers, Curr. Opin. Pharmacol. 2006, 6, 307-312.
5. I. Varela, S. Pereira, A. P. Ugalde, C. L. Navarro, M. F. Suárez, P. Cau, J. Cadiñanos, F. G. Osorio, N. Foray, J. Cobo, F. de Carlos, N. Lévy, J. M. P. Freije, C. Lõpez-Otín, Nat. Med. 2008, 14, 767-772.
6. X. Wang, E. R. Hinson, P. Cresswell, Cell Host Microbe 2007, 2, 96-105.
7. R. Docampo, S. N. Moreno, Curr. Drug Targets Infect. Disord. 2001, 1, 51-61.
8. M. Gnant, B. Mlineritsch, H. Stoeger, G. Luschin-Ebengreuth, D. Heck, C. Menzel, R. Jakesz, M. Seifert, M. Hubalek, G. Pristauz, T. Bauernhofer, H. Eidtmann, W. Eiermann, G. Steger, W. Kwasny, P. Dubsky, G. Hochreiner, E. P. Forsthuber, C. Fesl, R. Greil, et al., N. Engl. J. Med. 2009, 360, 679-691.
9. G. J. Morgan, Lancet 2010, 376, 1989-1999.
10. K. Thompson, M. J. Rogers, J. Bone Miner. Res. 2004, 19, 278-288.
11. R. E. Hewitt, A. Lissina, A. E. Green, E. S. Slay, D. A. Price, A. K. Sewell, Clin. Exp. Immunol. 2005, 139, 101-111.
12. J.-M. Rondeau, F. Bitsch, E. Bourgier, M. Geiser, R. Hemmig, M. Kroemer, S. Lehmann, P. Ramage, S. Rieffel, A. Strauss, J. R. Green, W. Jahnke, ChemMedChem 2006, 1, 267-273.
13. K. L. Kavanagh, K. Guo, J. E. Dunford, X. Wu, S. Knapp, F. H. Ebetino, M. J. Rogers, R. G. Russell, U. Oppermann, Proc. Natl. Acad. Sci. USA 2006, 103, 7829-7834.
14. M. S. Marma, Z. Xia, C. Stewart, F. Coxon, J. E. Dunford, R. Baron, B. A. Kashemirov, F. H. Ebetino, J. T. Triffitt, R. G. G. Russell, C. E. McKenna, J. Med. Chem. 2007, 50, 5967-5975.
15. Y. Zhang, R. Cao, F. Yin, M. P. Hudock, R.-T. Guo, K. Krysiak, S. Mukherjee, Y.-G. Gao, H. Robinson, Y. Song, J. H. No, K. Bergan, A. Leon, L. Cass, A. Goddard, T.-K. Chang, F.-Y. Lin, E. Van Beek, S. Papapoulos, A. H.-J. Wang, T. Kubo, M. Ochi, D. Mukkamala, E. Oldfield, J. Am. Chem. Soc. 2009, 131, 5153-5162.
16. Y. Zhang, R. Cao, F. Yin, F.-Y. Lin, H. Wang, K. Krysiak, J.-H. No, D. Mukkamala, K. Houlihan, J. Li, C. T. Morita, E. Oldfield, Angew. Chem. Int. Ed. 2010, 49, 1136-1138;
17. Angew. Chem. 2010, 122, 1154-1156.
18. Y.-S. Lin, J. Park, J. W. De Schutter, X. F. Huang, A. M. Berghuis, M. Sebag, Y. S. Tsantrizos, J. Med. Chem. 2012, 55, 3201-3215.
19. W. Jahnke, J.-M. Rondeau, S. Cotesta, A. Marzinzik, X. Pellé, M. Geiser, A. Strauss, M. Götte, F. Bitsch, R. Hemmig, C. Henry, S. Lehmann, J. F. Glickman, T. P. Roddy, S. J. Stout, J. R. Green, Nat. Chem. Biol. 2010, 6, 660-666.
20. S. Lindert, W. Zhu, Y.-L. Liu, R. Pang, E. Oldfield, J. A. McCammon, Chem. Biol. Drug Des. 2013, 81, 742-748;
21. Y.-L. Liu, R. Cao, Y. Wang, E. Oldfield, ACS Med. Chem. Lett. 2015, 6, 349-354.
22. J. W. Schmidberger, R. Schnell, G. Schneider, Acta Crystallogr. Sect. D 2015, 71, 721;
23. J. Liu, W. Liu, H. Ge, J. Gao, Q. He, L. Su, J. Xu, L.-q. Gu, Z.-s. Huang, D. Li, Biochim. Biophys. Acta 2014, 1840, 1051-1062.
24. J. W. De Schutter, J. Park, C. Y. Leung, P. Gormley, Y-S Lin, Z. Hu, A. M. Berghuis, J. Poirier, Y. S. Tsantrizos, J. Med. Chem. 2014, 57, 5764-5776.
25. W. Jahnke, G. Bold, A. Marzinzik, S. Ofner, X. Pellé, S. Cotesta, E. Bourgier, S. Lehmann, C. Henry, R. Hemmig, F. Stauffer, J. C. D. Hartwieg, J. R. Green, J.-M. Rondeau, Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201507064;
26. Angew. Chem. 2015, DOI: 10.1002/ange.201507064.
27. J. F. Glickman, A. Schmid, Assay Drug Dev. Technol. 2007, 5, 205-214.
28. M. Simonen, Y. Ibig-Rehm, G. Hofmann, J. Zimmermann, G. Albrecht, M. Magnier, V. Heidinger, D. Gabriel, J. Biomol. Screening 2008, 13, 456-467.
29. F. Cottet, M. Marull, O. Lefebvre, M. Schlosser, Eur. J. Org. Chem. 2003, 1559-1568.
30. G. Leclerc, G. Marciniak, N. Decker, J. Schwartz, J. Med. Chem. 1986, 29, 2433-2438.
31. H. Harada, O. Asano, T. Kawata, T. Inoue, T. Horizoe, N. Yasuda, K. Nagata, M. Murakami, J. Nagaoka, S. Kobayashi, I. Tanaka, S. Abe, Bioorg. Med. Chem. 2001, 9, 2709-2726.
32. J. R. Berenson, Curr. Opin. Support Palliat. Care 2011, 5, 233-240.
33. G. Morgan, A. Lipton, Semin. Oncol. 2010, 37, S 30-40.
34. H. K. Koul, S. Koul, R. B. Meacham, Prostate Cancer Prostatic Dis. 2012, 15, 111-119.
35. D. Santini, V. Virzi, M. E. Fratto, F. Bertoldo, R. Sabbatini, R. Berardi, N. Calipari, D. Ottaviani, T. Ibrahim, Curr. Cancer Drug Targets 2010, 10, 46-54.
36. M. Gnant, P. Clézardin, Cancer Treat. Rev. 2012, 38, 407-415.
37. J. E. Dunford, A. A. Kwaasi, M. J. Rogers, B. L. Barnett, F. H. Ebetino, R. G. G. Russell, U. Oppermann, K. L. Kavanagh, J. Med. Chem. 2008, 51, 2187-2195.
38. C. Ballatore, D. M. Huryn, A. B. Smith III, ChemMedChem 2013, 8, 385-395.
39. H. Maag, in Prodrugs: Challenges and Rewards (Eds.:, V. J. Stella, R. T. Borchardt, M. J. Hageman, R. Oliyai, H. Maag, J. Tilley,), Springer, New York, 2007, pp. 3-30.