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Structure-based design of potent CDK1 inhibitors derived from olomoucine

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Abstract

Cyclin-dependent kinase 1 (CDK1), an enzyme participating in the regulation of the cell cycle, constitutes a possible target in the search for new antitumor agents. Starting from the purine derivative olomoucine and following a structure-based approach, potent inhibitors of this enzyme were rapidly identified. The molecular modeling aspects of this work are described.

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References

  1. Morgan, D.O., Annu. Rev. Cell Dev. Biol., 13 (1997) 261.

    Google Scholar 

  2. Nasmyth, K., Science, 274 (1996) 1643.

    Google Scholar 

  3. Webster, K.R., Exp. Opin. Invest. Drugs, 7 (1998) 865.

    Google Scholar 

  4. Coleman, K.G., Lyssikatos, J.P. and Yang, B.V., Annu. Rep. Med. Chem., 32 (1997) 171.

    Google Scholar 

  5. Meijer, L., Trends Cell Biol., 6 (1996) 393.

    Google Scholar 

  6. Vesely, J., Havlicek, L., Strnad, M., Blow, J.J., Donella-Deana, A., Pinna, L., Letham, D.S., Kato, J.Y., Detivaud, L., Leclerc, S. and Meijer, L., Eur. J. Biochem., 224 (1994) 771.

    Google Scholar 

  7. Imbach, P., Capraro, H.G., Furet, P., Mett, H., Meyer, T. and Zimmermann, J., Bioorg. Med. Chem. Lett., 9 (1999) 91.

    Google Scholar 

  8. Hoessel, R., Leclerc, S., Endicott, J.A., Nobel, M.E.M., Lawrie, A., Tunnah, P., Leost, M., Damiens, E., Marie, D., Marko, D., Niederberger, E., Tang, W., Eisenbrand, G. and Meijer, L., Nat. Cell Biol., 1 (1999) 60.

    Google Scholar 

  9. Lawrie, A.M., Noble, M.E.M., Tunnah, P., Brown, N.R., Johnson, L.N. and Endicott, J.A., Nat. Struct. Biol., 4 (1997) 796.

    Google Scholar 

  10. De Azevedo, W.F., Leclerc, S., Meijer, L., Havlicek, L., Strnad, M. and Kim, S.H., Eur. J. Biochem., 243 (1997) 518.

    Google Scholar 

  11. De Azevedo, W.F., Mueller-Dieckmann, H.J., Schulze-Gahmen, U., Worland, P.J., Sausville, E. and Kim, S.H., Proc. Natl. Acad. Sci. USA, 93 (1996) 2735.

    Google Scholar 

  12. Schulze-Gahmen, U., Brandsen, J., Jones, H.D., Morgan, D.O., Meijer, L., Vesely, J. and Kim, S.H., Proteins: Struct. Funct. Genet., 22 (1995) 378.

    Google Scholar 

  13. De Bondt, H.L., Rosenblatt, J., Jancarik, J., Jones, H.D., Morgan, D.O. and Kim, S.H., Nature, 363 (1993) 595.

    Google Scholar 

  14. Dodin, G., Dreyfus, M. and Dubois, J.E., J. Chem. Soc. Perkin Trans. II, 4 (1979) 438.

    Google Scholar 

  15. Hanks, S.K. and Quinn, A.M., Methods Enzymol., 200 (1991) 38.

    Google Scholar 

  16. Johnson, L., Lowe, E.D., Noble, M.E.M. and Owen, D.J., FEBS Lett., 430 (1998) 1.

    Google Scholar 

  17. Taylor, S.S. and Radzio-Andzelm, E., Structure, 2 (1994) 345.

    Google Scholar 

  18. Mohamadi, F., Richards, N.G., Guida, W.C., Liskamp, R., Lipton, M., Caulfield, C., Chang, G., Hendrickson, T. and Still, W.C., J. Comput. Chem., 11 (1990) 440. (‘in house’ version enhanced for graphics by A. Dietrich-Unpublished results).

    Google Scholar 

  19. McDonald, D.Q. and Still, W.C., Tetrahedron Lett., 33 (1992) 7743.

    Google Scholar 

  20. Weiner, S.J., Kollman, P., Case, D.A., Singh, U.C., Ghio, C., Alagona, S., Profeta, S. and Weiner, P., J. Am. Chem. Soc., 106 (1984) 765.

    Google Scholar 

  21. Still, W.C., Tempczyk, A., Hawley, R.C. and Hendrickson, T., J. Am. Chem. Soc., 112 (1990) 6127.

    Google Scholar 

  22. Zimmermann, J., Buchdunger, E., Fabbro, D., Geiger, Th., Mett, H., Meyer, Th., Muller, M. and Ruetz, S., 215th ACS National Meeting, Dallas, TX, U.S.A., March 29-April 2, 1998.

  23. Zimmermann, J., Buchdunger, E., Fabbro, D., Geiger, Th., Mett, H., Meyer, Th., Muller, M. and Ruetz, S., 1st Italian-Swiss Meeting on Medicinal Chemistry, 1997.

  24. Legraverend, M., Ludwig, O., Bisagni, E., Leclerc, S., Meijer, L., Giocanti, N., Sadri, R. and Favaudon V., Bioorg. Med. Chem., 7 (1999) 1281.

    Google Scholar 

  25. Chang, Y.T., Gray, N.S., Rosania, G.R., Sutherlin, D.P., Kwon, S., Norman, T.C., Sarohia, R., Leost, M., Meijer, L. and Schultz, P.G., Chem. Biol., 6 (1999) 361.

    Google Scholar 

  26. Legraverend, M., Ludwig, O., Bisagni, E., Leclerc, S. and Meijer, L., Bioorg. Med. Chem. Lett., 8 (1998) 793.

    Google Scholar 

  27. Havlicek, L., Hanus, J., Vesely, J., Leclerc, S., Meijer, L., Shaw, G. and Strnad, M., J. Med. Chem., 40 (1997) 408.

    Google Scholar 

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Furet, P., Zimmermann, J., Capraro, HG. et al. Structure-based design of potent CDK1 inhibitors derived from olomoucine. J Comput Aided Mol Des 14, 403–409 (2000). https://doi.org/10.1023/A:1008115004986

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