Discovery of novel Cdc25 phosphatase inhibitors with micromolar activity based on the structure-based virtual screening

Journal of Medicinal Chemistry

Volumn 51, Issue 18, 2008, Pages 5533-5541

  Park, Hwangseo ^a   Young, Jae Bahn ^b   Jung, Suk Kyeong ^b   Dae, Gwin Jeong ^b   Lee, Sang Hyeup ^b   Seo, Il ^b   Yoon, Tae Sung ^b   Seung, Jun Kim ^b   Seong, Eon Ryu ^b  

^a Sejong University   (South Korea)

^b Korea Research Institute of Bioscience and Biotechnology (KRIBB)   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE INHIBITOR;

AMINO ACID SEQUENCE; ARTICLE; COMPUTER ANALYSIS; COMPUTER PROGRAM; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG SCREENING; ENZYME INHIBITION; IC 50; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; CATALYTIC DOMAIN; CDC25 PHOSPHATASES; CRYSTALLOGRAPHY, X-RAY; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; SEQUENCE HOMOLOGY, AMINO ACID; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 52449110024     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701157g     Document Type: Article

References (48)

1. Kristjansdottir, K.; Rudolph, J. Cdc25 phosphatases and cancer. Chem. Biol. 2004, 11, 1043-1051.
2. Rudolph, J. Cdc25 phosphatases: structure, specificity, and mechanism. Biochemistry 2007, 46, 3595-3604.
3. Galaktionov, K.; Lee, A. K.; Eckstein, J.; Draetta, G.; Meckler, J.; Loda, M.; Beach, D. Cdc25 phosphatases as potential human oncogenes. Science 1995, 269, 1575-1577.
4. Hernández, S.; Bessa, X.; Beá, S.; Hernández, L.; Nadal, A.; Mallofré, C.; Muntane, J.; Castells, A.; Fernández, P. L.; Cardesa, A.; Campo, E. Differential expression of Cdc25 cell-cycle- activating phosphatases in human colorectal carcinoma. Lab. Invest. 2001, 81, 465-473.
5. Takemara, I.; Yamamoto, H.; Sekimoto, M.; Ohue, M.; Noura, S.; Miyake, Y.; Matsumoto, T.; Aihara, T.; Tomita, N.; Tamaki, Y.; Sakita, I.; Kikkawa, N.; Matsuura, N.; Shiozaki, H.; Monden, M. Overexpression of Cdc25B phosphatase as a novel marker of poor prognosis of human colorectal carcinoma. Cancer Res. 2000, 60, 3043-3050.
6. Hernandez, S.; Hernandez, L.; Bea, S.; Pinyol, M.; Nayach, I.; Bellosillo, B.; Nadal, A.; Ferrer, A.; Fernandez, P. L.; Montserrat, E.; Cardesa, A.; Cardes, E.; Campo, E. Cdc25A and the splicing variant Cdc25B2, but not Cdc25B 1, -B3 or -C, are overexpressed in aggressive human non-Hodgkin's lymphomas. Int. J. Cancer 2000, 89, 148-152.
7. Ngan, E. S. W.; Hashimoto, Y.; Ma, Z.-Q.; Tsai, M. J.; Tsai, S. Y. Overexpression of Cdc25B, an androgen receptor coactivator, in prostate cancer. Oncogene 2003, 22, 734-739.
8. Guo, J.; Kleeff, J.; Li, J.; Ding, J.; Hammer, J.; Zhao, Y.; Giese, T.; Korc, M.; Büchler, M. W.; Friess, H. Expression and functional significance of Cdc25B in human pancreatic ductal adenocarcinoma. Oncogene 2004, 23, 71-81.
9. Wu, W. G.; Fan, Y. H.; Kemp, B. L.; Walsh, G.; Mao, L. Overexpression of Cdc25A and cdc25B is frequent in primary nonsmall cell lung cancer but is not associated with overexpression of c-myc. Cancer Res. 1998, JS, 4082-4085.
10. Sasaki, H.; Yukiue, H.; Kobayashi, Y.; Tanahashi, M.; Moriyama, S.; Nakashima, Y.; Fukai, I.; Kiriyama, M.; Yamakawa, Y.; Fujii, Y. Expression of the Cdc25B gene as a prognosis marker in non-small cell lung cancer. Cancer Lett. 2001, 775, 187-192.
11. Fernandez-Vidal, A.; Ysebaert, L.; Didier, C; Betous, R.; Toni, F. D.; Prade-Houdellier, N.; Demur, C; Contour-Galcéra, M.-O.; Prévost, G. P.; Ducommun, B.; Payrastre, B.; Racaud-Sultan, C.; Manenti, S. Cell adhesion regulates Cdc25A expression and proliferation in acute myeloid leukemia. Cancer Res. 2006, 66, 7128-7135.
12. Nishikawa, Y.; Carr, B. I.; Wang, M.; Kar, S.; Finn, F.; Dowd, B.; Zheng, Z. B.; Kerns, J.; Naganathan, S. Growth inhibition of hepatoma cells induced by vitamin K and its analogs. J. Biol. Chem. 1995, 270, 28304-28310.
13. Boutros, R.; Dozier, C.; Ducommun, B. The when and wheres of Cdc25 phosphatases. Curr. Opin. Cell Biol. 2006, 18, 185-191.
14. Fauman, E. B.; Cogswell, J. P.; Lovejoy, B.; Rocque, W. J.; Holmes, W.; Montana, V. G.; Piwnica-Worms, H.; Rink, M. J.; Saper, M. A. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell 1998, 93, 617-625.
15. 2/M phase transition of the cell cycle. J. Mol. Biol. 1999, 293, 559-568.
16. Contour-Galcéra, M.-O.; Sidhu, A.; Prévost, G.; Bigg, D.; Ducommun, B. What's new on Cdc25 phosphatase inhibitors. Pharmcol. Ther. 2007, 115, 1-12.
17. Ham, S. W.; Carr, B. I. Cell division cycle 25 (Cdc25) phosphatase inhibitors as antitumor agents. Drug Des. Rev. 2004, 1, 123-132.
18. Prevost, G. P.; Brezak, M.-C.; Goubin, F.; Mondesert, O.; Galcera, M.-O.; Quaranta, M.; Alby, F.; Lavergne, O.; Ducommun, B. Prog. Cell Cycle Res. 2003, 5, 225-234.
19. Lazo, J. S.; Asian, D. C.; Southwick, E. C.; Cooley, K. A.; Ducruet, A. P.; Joo, B.; Vogt, A.; Wipf, P. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25. J. Med. Chem. 2001, 44, 4042-4049.
20. Sohn, J.; Kiburz, B.; Li, Z.; Deng, L.; Safi, A.; Pirrung, M. C.; Rudolph, J. Inhibition of Cdc25 phosphatases by indolyldihydroxyquinones. J. Med. Chem. 2003, 46, 2580-2588.
21. Brault, L.; Denancé, M.; Banaszak, E.; Maadidi, S. E.; Battaglia, E.; Bagrel, D.; Samadi, M. Synthesis and biological evaluation of dialkylsubstituted maleic anhydrides as novel inhibitors of Cdc25 dual specificity phosphatases. Eur. J. Med. Chem. 2007, 42, 243-247.
22. Huang, W.; Li, J.; Zhang, W.; Zhou, Y.; Xie, C.; Luo, Y.; Li, Y.; Wang, J.; Li, J.; Lu, W. Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases. Bioorg. Med. Chem. Lett. 2006, 16, 1905-1908.
23. Brun, M.-P.; Braud, E.; Angotti, D.; Mondesert, O.; Quaranta, M.; Montes, M.; Miteva, M.; Gresh, N.; Ducommun, B.; Garbay, C. Design, synthesis, and biological evaluation of novel naphthoquinone derivatives with Cdc25 phosphatase inhibitory activity. Bioorg. Med. Chem. 2005, 13, 4871-4879.
24. Contour-Galcéra, M.-O.; Lavergne, O.; Brezak, M.-C.; Ducommun, B.; Prévost, G. Synthesis of small molecule CDC25 phosphatases inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 5809-5812.
25. Lazo, J. S.; Nemoto, K.; Pestell, K. E.; Cooley, K.; Southwick, E. C.; Mitchell, D. A.; Furey, W.; Gussio, R.; Zaharevitz, D. W.; Joo, B.; Wipf, P. Identification of a potent and selective pharmacophores for Cdc25 dual specificity phosphatase inhibitors. Mol. Pharmacol. 2002, 61, 720-728.
26. Lavecchia, A.; Cosconati, S.; Limongelli, V.; Novellino, E. Modeling of Cdc25B dual specificity protein phosphatase inhibitors: docking of ligands and enzymatic inhibition mechanism. ChemMedChem 2006, 1, 540-550.
27. Park, H.; Carr, B. I.; Li, M.; Ham, S. W. Fluorinated NSC as a Cdc25 inhibitor. Bioorg. Med. Chem. Lett. 2007, 17, 2351-2354.
28. Warren, G. L.; Andrews, C. W.; Capelli, A.-M.; Clarke, B.; LaLonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Wall, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. J. Med. Chem. 2006, 49, 5912-5931.
29. Zou, X.; Sun, Y.; Kuntz, I. D. Inclusion of solvation in ligand binding free energy calculations using generalized-Born model. J. Am. Chem. Soc. 1999, 121, 8033-8043.
30. Shoichet, B. K.; Leach, A. R.; Kuntz, I. D. Ligand solvation in molecular docking. Proteins 1999, 34, 4-16.
31. With respect to the numbering scheme for the amino acids, we followed those used in the X-ray crystallographic studies of Cdc25A (ref 14) and Cdc25B (ref 15).
32. Baker, D.; Sali, A. Protein structure prediction and structural genomics. Science 2001, 294, 93-96.
33. Bairoch, A.; Apweiler, R. The SWISS-PROT protein sequence data bank and its supplement TrEMBL in 1999. Nucleic Acids Res. 1999, 27, 49-54.
34. Thompson, J. D.; Higgins, D. G.; Gibson, T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22, 4673-4680.
35. Sali, A.; Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 1993, 234, 779-815.
36. Fiser, A.; Do, R. K. G.; Sali, A. Modeling of loops in protein structures. Protein Sci. 2000, 9, 1753-1773.
37. Sippl, M. J. Recognition of errors in three-dimensional structures of proteins. Proteins 1993, 17, 355-362.
38. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998, 19, 1639-1662.
39. Park, H.; Lee, J.; Lee, S. Critical assessment of the automated AutoDock as a new docking tool for virtual screening. Proteins 2006, 65, 549-554.
40. Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford University Press: Oxford, U.K., 1997.
41. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 1997, 23, 3-25.
42. Gasteiger, J.; Marsili, M. Iterative partial equalization of orbital electronegativity - a rapid access to atomic charges. Tetrahedron 1980, 36, 3219-3228.
43. Mehler, E. L.; Solmajer, T. Electrostatic effects in proteins: comparison of dielectric and charge models. Protein Eng. 1991, 4, 903-910.
44. Stouten, P. F. W.; Frömmel, C.; Nakamura, H.; Sander, C. An effective solvation term based on atomic occupancies for use in protein simulations. Mol. Simul. 1993, 10, 97-120.
45. Kang, H.; Choi, H.; Park, H. Prediction of molecular solvation free energy based on the optimization of atomic solvation parameters with genetic algorithm. J. Chem. Inf. Model. 2007, 47, 509-514.
46. Tamura, K.; Southwick, E. C.; Kerns, J.; Rosi, K.; Carr, B. I.; Wilcox, C.; Lazo, J. S. Cdc25 inhibition and cell cycle arrest by a synthetic thioalkyl vitamin K analogue. Cancer Res. 2000, 60, 1317-1325.
47. Osada, S.; Osada, K.; Carr, B. I. Tumor cell growth inhibition and extracellular signal-regulated kinase (ERK) phosphorylation by novel K vitamins. J. Mol. Biol. 2001, 314, 765-772.
48. Rice, R. L.; Rusnak, J. M.; Yokokawa, F.; Yokokawa, S.; Messner, D. J.; Boynton, A. L.; Wipf, P.; Lazo, J. S. A targeted library of small-molecule, tyrosine, and dual-specificity phosphatase inhibitors derived from a rational core design and random side chain variation. Biochemistry 1997, 36, 15965-15974.