MDM2/MDMX inhibitor peptide: WO2008106507

Expert Opinion on Therapeutic Patents

Volumn 19, Issue 5, 2009, Pages 721-726

  Macchiarulo, Antonio ^b   Pellicciari, Roberto ^a,b  

^a UNIVERSITY OF PERUGIA   (Italy)

^b Dipartimento di Chimica e Tecnologia del Farmaco   (Italy)

Author keywords

MDM2; MDMX; p53; Peptidomimetics

Indexed keywords

ANTINEOPLASTIC AGENT; MDM2 INHIBITOR; MDMX INHIBITOR; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P53; UNCLASSIFIED DRUG;

APOPTOSIS; DRUG BINDING; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; HYDROPHOBICITY; IN VITRO STUDY; IN VIVO STUDY; MEDICAL RESEARCH; REVIEW; TUMOR CELL; TUMOR GROWTH;

ANTINEOPLASTIC AGENTS; APOPTOSIS; DRUG DESIGN; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; NEOPLASMS; NUCLEAR PROTEINS; PATENTS AS TOPIC; PEPTIDES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR SUPPRESSOR PROTEIN P53;

EID: 67649360325     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543770902755137     Document Type: Review

References (35)

1. Meulmeester E, Jochemsen AG. p53: a guide to apoptosis. Curr Cancer Drug Targets 2008;8(2):87-97 • A review on p53 pathways to apoptosis.
2. Toledo F, Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 2006;6(12):909-923 •• A review on the regulatory functions of MDM2 and MDMX. (Pubitemid 44862676)
3. Barboza JA, Iwakuma T, Terzian T, et al. Mdm2 and Mdm4 loss regulates distinct p53 activities. Mol Cancer Res 2008;6(6):947-954
4. Marine JC, Francoz S, Maetens M, et al. Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4. Cell Death Differ 2006;13(6):927-934 (Pubitemid 43753483)
5. Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol 2007;8(4):275-283
6. Toledo F, Wahl GM. MDM2 and MDM4: p53 regulators as targets in anticancer therapy. Int J Biochem Cell Biol 2007;39(7-8):1476-1482 (Pubitemid 47031042)
7. Halatsch ME, Schmidt U, Unterberg A, Vougioukas VI. Uniform MDM2 overexpression in a panel of glioblastoma multiforme cell lines with divergent EGFR and p53 expression status. Anticancer Res 2006;26(6B):4191-4194 (Pubitemid 46031490)
8. Laurie NA, Shih CS, Dyer MA. Targeting MDM2 and MDMX in retinoblastoma. Curr Cancer Drug Targets 2007;7(7):689-695 (Pubitemid 350074972)
9. Laurie NA, Donovan SL, Shih CS, et al. Inactivation of the p53 pathway in retinoblastoma. Nature 2006;444(7115):61-66 (Pubitemid 44684754)
10. Patel S, Player MR. Small-molecule inhibitors of the p53-HDM2 interaction for the treatment of cancer. Expert Opin Investig Drugs 2008;17(12):1865-1882
11. Vassilev LT. MDM2 inhibitors for cancer therapy. Trends Mol Med 2007;13(1):23-31 • A comprehensive review on available inhibitors of MDM2. (Pubitemid 46027725)
12. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004;303(5659):844-848
13. Hu B, Gilkes DM, Farooqi B, et al. MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem 2006;281(44):33030-33035 • The first evidence that Nutlins are inefficient for the disruption of MDMX-p53 interaction and unable to activate p53 in cells overexpressing MDMX. (Pubitemid 46036685)
14. Gilkes DM, Chen J. Distinct roles of MDMX in the regulation of p53 response to ribosomal stress. Cell Cycle 2007;6(2):151-155 (Pubitemid 46232494)
15. Marine JC, Dyer MA, Jochemsen AG. MDMX: from bench to bedside. J Cell Sci 2007;120(Pt 3):371-378 (Pubitemid 46332500)
16. Hu B, Gilkes DM, Chen J. Efficient p53 activation and apoptosis by simultaneous disruption of binding to MDM2 and MDMX. Cancer Res 2007;67(18):8810-8817 •• The disclosure of the first dual MDM2/MDMX inhibitor peptide. (Pubitemid 47437457)
17. Bottger A, Bottger V, Sparks A, et al. Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo. Curr Biol 1997;7(11):860-869 (Pubitemid 27493125)
18. Bottger V, Bottger A, Howard SF, et al. Identification of novel mdm2 binding peptides by phage display. Oncogene 1996;13(10):2141-2147 (Pubitemid 26411564)
19. Bottger A, Bottger V, Garcia-Echeverria C, et al. Molecular characterization of the hdm2-p53 interaction. J Mol Biol 1997;269(5):744-756 (Pubitemid 27280843)
20. Kussie PH, Gorina S, Marechal V, et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 1996;274(5289):948-953 (Pubitemid 26398409)
21. Popowicz GM, Czarna A, Rothweiler U, et al. Molecular basis for the inhibition of p53 by Mdmx. Cell Cycle 2007;6(19):2386-2392 (Pubitemid 350064092)
22. Popowicz GM, Czarna A, Holak TA. Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain. Cell Cycle 2008;7(15):2441-2443
23. Gasteiger E, Hoogland C, Gattiker A, et al. Protein Identification and Analysis Tools on the ExPASy Server. In: WJ, M. editor, The proteomics protocols handbook: Humana Press 2005. p. 571-607
24. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol 1982;157(1):105-132
25. Bhaskaran R, Ponnuswammy PK. Positional flexibilities of amino acid residues in globular proteins. Int J Pept Protein Res 1988;32:242-255
26. Zimmerman JM, Eliezer N, Simha R. The characterization of amino acid sequences in proteins by statistical methods. J Theor Biol 1968;21:170-201
27. Macchiarulo A, Pellicciari R. Exploring the other side of biologically relevant chemical space: insights into carboxylic, sulfonic and phosphonic acid bioisosteric relationships. J Mol Graph Model 2007;26(4):728-739 (Pubitemid 47615556)
28. Parker AL, Nicklin SA, Baker AH. Interactions of adenovirus vectors with blood: implications for intravascular gene therapy applications. Curr Opin Mol Ther 2008;10(5):439-448
29. Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 2007;450(7172):1001-1009 (Pubitemid 350273630)
30. Fischer PM, Lane DP. Small-molecule inhibitors of the p53 suppressor HDM2: have protein-protein interactions come of age as drug targets? Trends Pharmacol Sci 2004;25(7):343-346
31. Arkin MR, Wells JA. Small-molecule inhibitors of proteinprotein interactions: progressing towards the dream. Nat Rev Drug Discov 2004;3(4):301-317 (Pubitemid 38499758)
32. Berg T. Small-molecule inhibitors of protein-protein interactions. Curr Opin Drug Discov Devel 2008;11(5):666-674
33. Secchiero P, di Iasio MG, Gonelli A, Zauli G. The MDM2 inhibitor Nutlins as an innovative therapeutic tool for the treatment of haematological malignancies. Curr Pharm Des 2008;14(21):2100-2110
34. Corallini F, Celeghini C. The potential role of Nutlins in the treatment of B-chronic lymphocytic leukemia (B-CLL). J Leukoc Biol 2008;84(3):651
35. 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 USA 2008;105(10):3933-3938 (Pubitemid 351723502)