New players in cancer therapeutics: Focus on inhibitors of MDM2-P53 protein-protein interaction

Drugs of the Future

Volumn 37, Issue 4, 2012, Pages 273-281

  Capdevila, J ^a   Cervantes, A ^b   Tabernero, Josep ^a  

^a VALL D HEBRON UNIVERSITY HOSPITAL   (Spain)

^b UNIVERSITY OF VALENCIA   (Spain)

Author keywords

CYC 700; MI 219; Nutlins; Oncoprotein Mdm2; p53; RG 7112; Serdemetan

Indexed keywords

5 DEAZAFLAVINE DERIVATIVE; JNJ 27065909; JNJ 27291199; MI 219; MI 319; MI 43; MI 63; NSC 652287; NUTLIN 1; NUTLIN 2; NUTLIN 3; PROTEIN INHIBITOR; PROTEIN MDM2; PROTEIN P53; PXN 727; PXN 822; RO 5045337; SERDEMETAN; TRYPTAMINE DERIVATIVE; UNCLASSIFIED DRUG;

ANOREXIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CELL CYCLE REGULATION; CELL DAMAGE; DNA DAMAGE; DNA REPAIR; DRUG DOSE ESCALATION; FATIGUE; HUMAN; LIVER DISEASE; NAUSEA; NONHUMAN; PROTEIN PROTEIN INTERACTION; QT PROLONGATION; REVIEW; UPREGULATION; VOMITING;

EID: 84952977785     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2012.037.04.1769833     Document Type: Review

References (47)

1. Vogelstein, B., Lane, D., Levine, A.J. Surfing the p53 network. Nature 2000, 408(6810): 307-10.
2. Susin, S.A., Daugas, E., Ravagnan, L. et al. Two distinct pathways leading to nuclear apoptosis. J Exp Med 2000, 192(4): 571-80.
3. Hainaut, P., Hollstein, M. p53 and human cancer: The first ten thousand mutations. Adv Cancer Res 2000, 77: 81-137. (Pubitemid 29439303)
4. Li, F.P., Fraumeni, J.F. Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 1969, 71(4): 747-52.
5. Malkin, D., Li, F.P., Strong, L.C. et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990, 250(4985): 1233-8. (Pubitemid 120031831)
6. Momand, J., Zambetti, G.P., Olson, D.C., George, D., Levine, A.J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 1992, 69(7): 1237-45.
7. Freedman, D.A., Wu, L., Levine, A.J. Functions of the MDM2 oncoprotein. Cell Mol Life Sci 1999, 55(1): 96-107. (Pubitemid 29077858)
8. Wu, X., Bayle, J.H., Olson, D., Levine, A.J. The p53-mdm-2 autoregulatory feedback loop. Genes Dev 1993, 7(7A): 1126-32. (Pubitemid 23207405)
9. Kussie, P.H., Gorina, S., Marechal, V. et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 1996, 274(5289): 948-53. (Pubitemid 26398409)
10. Haupt, Y., Maya, R., Kazaz, A., Oren, M. Mdm2 promotes the rapid degradation of p53. Nature 1997, 387(6630): 296-9. (Pubitemid 27220766)
11. Zhang, Y., Xiong, Y., Yarbrough, W.G. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 1998, 92(6): 725-34. (Pubitemid 28155312)
12. Bond, G.L., Levine, A.J. A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans. Oncogene 2007, 26(9): 1317-23. (Pubitemid 46328460)
13. Wang, H., Zeng, X., Oliver, P. et al. MDM2 oncogene as a target for cancer therapy: An antisense approach. Int J Oncol 1999, 15(4): 653-60.
14. Lai, Z., Yang, T., Kim, Y.B. et al. Differentiation of Hdm2-mediated p53 ubiquitination and Hdm2 autoubiquitination activity by small molecular weight inhibitors. Proc Natl Acad Sci U S A 2002, 99(23): 14734-9. (Pubitemid 35334553)
15. Midgley, C.A., Desterro, J.M., Saville, M.K. et al. An N-terminal p14ARF peptide blocks Mdm2-dependent ubiquitination in vitro and can activate p53 in vivo. Oncogene 2000, 19(19): 2312-23. (Pubitemid 30307207)
16. 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(9): 2523-9. (Pubitemid 24254027)
17. Shangary, S., Qin, D., McEachern, D. et al. Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci U S A 2008, 105(10): 3933-8. (Pubitemid 351723502)
18. Smith, M.A., Gorlick, R., Kolb, E.A. et al. Initial testing of JNJ-26854165 (serdemetan) by the pediatric preclinical testing program. Pediatr Blood Cancer 2011, Epub ahead of print.
19. Kojima, K., Burks, J.K., Arts, J., Andreeff, M. The novel tryptamine derivative JNJ-26854165 induces wild-type p53- and E2F1-mediated apoptosis in acute myeloid and lymphoid leukemias. Mol Cancer Ther 2010, 9(9): 2545-57.
20. Chene, P., Fuchs, J., Bohn, J., Garcia-Echeverria, C., Furet, P., Fabbro, D. A small synthetic peptide, which inhibits the p53-hdm2 interaction, stimulates the p53 pathway in tumour cell lines. J Mol Biol 2000, 299(1): 245- 53.
21. Ventura, A., Kirsch, D.G., McLaughlin, M.E. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 2007, 445(7128): 661-5. (Pubitemid 46232887)
22. Vassilev, L.T. Small-molecule antagonists of p53-MDM2 binding: Research tools and potential therapeutics. Cell Cycle 2004, 3(4): 419-21. (Pubitemid 40278226)
23. Vassilev, L.T., Vu, B.T., Graves, B. et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004, 303(5659): 844-8. (Pubitemid 38174664)
24. Van Maerken, T., Ferdinande, L., Taildeman, J. et al. Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J Natl Cancer Inst 2009, 101(22): 1562-74.
25. Tabe, Y., Sebasigari, D., Jin, L. et al. MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma. Clin Cancer Res 2009, 15(3): 933-42.
26. Tovar, C., Rosinski, J., Filipovic, Z. et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy. Proc Natl Acad Sci U S A 2006, 103(6): 1888-93. (Pubitemid 43228788)
27. Canner, J.A., Sobo, M., Ball, S. et al. MI-63: A novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53. Br J Cancer 2009, 101(5): 774-81.
28. Shangary, S., Ding, K., Qiu, S. et al. Reactivation of p53 by a specific MDM2 antagonist (MI-43) leads to p21-mediated cell cycle arrest and selective cell death in colon cancer. Mol Cancer Ther 2008, 7(6): 1533-42.
29. Mohammad, R.M., Wu, J., Azmi, A.S. et al. An MDM2 antagonist (MI-319) restores p53 functions and increases the life span of orally treated follicular lymphoma bearing animals. Mol Cancer 2009, 8: 115.
30. Grasberger, B.L., Lu, T., Schubert, C. et al. Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. J Med Chem 2005, 48(4): 909-12. (Pubitemid 40270436)
31. Rothweiler, U., Czarna, A., Krajewski, M. et al. Isoquinolin-1-one inhibitors of the MDM2-p53 interaction. ChemMedChem 2008, 3(7): 1118-28.
32. Nieves-Neira, W., Rivera, M.I., Kohlhagen, G. et al. DNA protein crosslinks produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells. Mol Pharmacol 1999, 56(3): 478-84. (Pubitemid 29406874)
33. Wilson, J.M., Henderson, G., Black, F. et al. Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells. Bioorg Med Chem 2007, 15(1): 77-86. (Pubitemid 44738595)
34. Issaeva, N., Bozko, P., Enge, M. et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 2004, 10(12): 1321-8. (Pubitemid 40022713)
35. Yang, Y., Ludwig, R.L., Jensen, J.P. et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 2005, 7(6): 547-59. (Pubitemid 40799248)
36. Arts, J., Page, M., Valckx, A. et al. JNJ-26854165 - A novel hdm2 antagonist in clinical development showing broad-spectrum preclinical antitumor activity against solid malignancies. Proc Am Assoc Cancer Res (AACR) 2008, 49: Abst 1592.
37. Tabernero, J., Dirix, L., Schoffski, P. et al. A phase I first-in-human pharmacokinetic and pharmacodynamic study of serdemetan in patients with advanced solid tumors. Clin Cancer Res 2011, 17(19): 6313-21.
38. thAnnu Meet Am Soc Clin Oncol (ASCO) (June 3-7, Chicago) 2011, Abst 3039.
39. th Annu Meet Am Soc Clin Oncol (ASCO) (June 3-7, Chicago) 2011, Abst 10007b.
40. Secchiero, P., Corallini, F., Gonelli, A. et al. Antiangiogenic activity of the MDM2 antagonist nutlin-3. Circ Res 2007, 100(1): 61-9. (Pubitemid 46066774)
41. Secchiero, P., Barbarotto, E., Tiribelli, M. et al. Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin- 3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood 2006, 107(10): 4122-9. (Pubitemid 43726822)
42. Kastan, M.B. Wild-type p53: Tumors can't stand it. Cell 2007, 128(5): 837- 40.
43. Bottger, V., Bottger, A., Garcia-Echeverria, C. et al. Comparative study of the p53-mdm2 and p53-MDMX interfaces. Oncogene 1999, 18(1): 189-99. (Pubitemid 29060593)
44. Jackson, M.W., Berberich, S.J. MdmX protects p53 from Mdm2-mediated degradation. Mol Cell Biol 2000, 20(3): 1001-7. (Pubitemid 30044237)
45. Patton, J.T., Mayo, L.D., Singhi, A.D., Gudkov, A.V., Stark, G.R., Jackson, M.W. Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Cancer Res 2006, 66(6): 3169-76.
46. Jones, R.J., Baladandayuthapani, V., Neelapu, S. et al. HDM-2 inhibition suppresses expression of ribonucleotide reductase subunit M2, and synergistically enhances gemcitabine-induced cytotoxicity in mantle cell lymphoma. Blood 2011, 118(15): 4140-9.
47. Secchiero, P., Zerbinati, C., di Iasio, M.G. et al. Synergistic cytotoxic activity of recombinant TRAIL plus the non-genotoxic activator of the p53 pathway nutlin-3 in acute myeloid leukemia cells. Curr Drug Metab 2007, 8(4): 395-403. (Pubitemid 46780067)