Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction

Journal of Medicinal Chemistry

Volumn 49, Issue 12, 2006, Pages 3432-3435

  Ding, Ke ^a   Lu, Yipin ^a   Nikolovska Coleska, Zaneta ^a   Wang, Guoping ^a   Qiu, Su ^a   Shangary, Sanjeev ^a   Gao, Wei ^a   Qin, Dongguang ^a   Stuckey, Jeanne ^b   Krajewski, Krzysztof ^c   Roller, Peter P ^c   Wang, Shaomeng ^a  

^a UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MI 63; ONCOPROTEIN; OXINDOLE; PROTEIN BCL 2; PROTEIN BCL X; PROTEIN INHIBITOR; PROTEIN MDM2; PROTEIN P53; SPIROOXINDOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; CANCER CELL; CANCER INHIBITION; CELL GROWTH; CELL STRAIN LNCAP; CHIRALITY; CONTROLLED STUDY; DRUG DESIGN; GENE ACTIVATION; HUMAN; HUMAN CELL; HYDROPHOBICITY; IC 50; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; STRUCTURE ACTIVITY RELATION; TARGET CELL;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL MEMBRANE PERMEABILITY; CRYSTALLOGRAPHY, X-RAY; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INDOLES; MODELS, MOLECULAR; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-MDM2; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR SUPPRESSOR PROTEIN P53;

EID: 33745154819     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm051122a     Document Type: Article

References (19)

1. Levine, A. J. p53, the cellular gatekeeper for growth and division. Cell 1997, 88, 323-331.
2. Vogelstein, B.; Lane, D.; Levine, A. J. Surfing the p53 network. Nature 2000, 408, 6810, 307-310.
3. Vousden, K. H.: Lu, X. Live or let die: the cell's response to p53. Nat. Rev. Cancer 2002, 2, 594-604.
4. Hainaut, P.; Hollstein, M. p53 and human cancer: the first ten thousand mutations. Adv. Cancer Res. 2000, 77, 81-137.
5. Wu, X.; Bayle, J. H.; Olson, D.; Levine, A. J. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 1993, 7 (7A), 1126-1132.
6. Chene, P. Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat. Rev. Cancer 2003, 3, 102-109.
7. Vassilev, L. T. p53 activation by small molecules: application in oncology. J. Med. Chem. 2005, 48, 4491-4499.
8. Vassilev, L. T.; Vu, B. T.; Graves, B.; Carvajal, D.; Podlaski, F.; Filipovic, Z.; Kong, N.; Kammlott, U.; Lukacs, C.; Klein, C.; Fotouhi, N.; Liu, E. A. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004, 303, 844-848.
9. Ding, K.; Lu, Y.; Nikolovska-Koleska, Z.; Qiu, S.; Ding Y.; Gao, W.; Stuckey, J.; Roller, P. P., Tomita, Y.; Deschamps, J. R.; Wang, S. Structure-based design of potent non-peptide MDM2 inhibitors. J. Am. Chem. Soc. 2005, 127, 10130-10131.
10. Grasberger, B. L.; Lu, T.; Schubert, C.; Parks, D. I.; Carver, T. E.; Koblish, H. K.; Cummings, M. D.; LaFrance, L. V.; Milkiewicz, K. L.; Calvo, R. R.; Maguire, D.; Lattanze, I.; Franks, C. F.; Zhao, S.; Ramachandren, K.; Bylebyl, G. R.; Zhang, M.; Manthey, C. L.; Petrella, E. C.; Pantoliano, M. W.; Deckman, I. C.; Spurlino, J. C.; Maroney, A. C.; Tomczuk, B. E.; Molloy, C. J.; Bone, R. F. Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. J. Med. Chem. 2005, 48, 909-912.
11. Yin, H.; Lee, G.-I.; Park, H.-S.; Payne, G. A.; Rodriguez, J. M.; Sebti, S. M.; Hamilton, A. D. Terphenyl-based helical mimetics that disrupt the p53/HDM2 Interaction. Angew. Chem., Int. Ed. 2005, 44, 2704-2707.
12. Kussie, P. H.; Gorina, S.; Marechal, V.; Elenbaas, B.; Moreau, J.; Levine, A. J.; Pavletich, N. P. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 1996, 274, 948-953.
13. Garcia-Echeverria, C.; Chene, P.; Blommers, M. J. J.; Furet, P. Discovery of potent antagonists of the interaction between human double minute 2 and tumor suppressor p53. J. Med. Chem. 2000, 43, 3205-3208.
14. Lin, J.; Chen, B.; Elenbass, B.; Levine, A. J. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev. 1994, 8, 1235-1246.
15. Picksley, S. M.; Vojtesek, B.; Sparks, A.; Lane, D. P. Immunochemical analysis of the interaction of p53 with MDM2;-fine mapping of the MDM2 binding site on p53 using synthetic peptides. Oncogene 1994, 9, 2523-2529.
16. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.
17. Ding, K.; Wang, G.; Deschamps, J. R.; Parrish, D. A.; Wang, S. Synthesis of spirooxindoles via asymmetric 1,3-dipolar cycloaddition. Tetrahedron Lett. 2005, 46, 5949-5951.
18. Oltersdorf, T.; Elmore, S. W.; Shoemaker, A. R.; Armstrong, R. C.; Augeri, D. J.; Belli, B. A.; Bruncko, M.; Deckwerth, T. L.; Dinges, J.; Hajduk, P. J.; Joseph, M. K.; Kitada, S.; Korsmeyer, S. J.; Kunzer, A. R.; Letai, A.; Li, C.; Mitten, M. J.; Nettesheim, D. G.; Ng, S.; Nimmer, P. M.; O'Connor, J. M.; Oleksijew, A.; Petros, A. M.; Reed, J. C.; Shen, W.; Tahir, S. K.; Thompson, C. B.; Tomaselli, K. J.; Wang, B.; Wendt, M. D.; Zhang, H.; Fesik, S. W.; Rosenberg, S. H. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005, 435, 677-681.
19. Fan, R.; Kumaravel, T. S.; Jalali, F.; Marrano, P.; Squire, J. A.; Bristow, R. G. Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression. Cancer Res. 2004, 64, 8526-8533.