Small-molecule inhibitors of the p53 suppressor HDM2: Have protein-protein interactions come of age as drug targets?

Trends in Pharmacological Sciences

Volumn 25, Issue 7, 2004, Pages 343-346

  Fischer, Peter M ^a   Lane, David P ^a  

^a CYCLACEL LTD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; BENZODIAZEPINE DERIVATIVE; CHALCONE DERIVATIVE; PEPTIDE DERIVATIVE; PROTEIN MDM2; PROTEIN P53; REGULATOR PROTEIN; SUPPRESSOR FACTOR; TRYPTOPHAN DERIVATIVE; UNCLASSIFIED DRUG;

ALPHA HELIX; AMINO TERMINAL SEQUENCE; APOPTOSIS; BINDING AFFINITY; CANCER GROWTH; DRUG BINDING SITE; DRUG TARGETING; GENE OVEREXPRESSION; GROWTH INHIBITION; HUMAN; MEMBRANE PERMEABILITY; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; SITE DIRECTED MUTAGENESIS; TRANSCRIPTION INITIATION; WILD TYPE;

EID: 3042523534     PISSN: 01656147     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tips.2004.04.011     Document Type: Short Survey

References (25)

1. Vogelstein B., et al. Surfing the p53 network. Nature. 408:2000;307-310
2. Momand J., et al. The MDM2 gene amplification database. Nucleic Acids Res. 26:1998;3453-3459
3. García-Echeverría C., et al. Discovery of potent antagonists of the interaction between human double minute 2 and tumor suppressor p53. J. Med. Chem. 43:2000;3205-3208
4. Chène P., et al. A small synthetic peptide, which inhibits the p53-hdm2 interaction, stimulates the p53 pathway in tumour cell lines. J. Mol. Biol. 299:2000;245-253
5. Duncan S.J., et al. Isolation and structure elucidation of chlorofusin, a novel p53-MDM2 antagonist from a Fusarium sp. J. Am. Chem. Soc. 123:2001;554-560
6. Chene P. Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat. Rev. Cancer. 3:2003;102-109
7. Kussie P.H., et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science. 274:1996;948-953
8. Galatin P.S., Abraham D.J. QSAR: hydropathic analysis of inhibitors of the p53-MDM2 interaction. Proteins. 45:2001;169-175
9. Zheleva D.I., et al. The p53-Mdm2 pathway: targets for the development of new anticancer therapeutics. Mini Rev. Med. Chem. 3:2003;257-270
10. Luke, R.W.A., et al. (2000) Preparation of amino acid and peptidyl piperazine-4-phenyl derivatives as inhibitors of the interaction between MDM2 and p53. PCT Int. Pat. Appl. Publ. WO 2000015657, Zeneca Ltd., UK.
11. Luke R.W.A., et al. Design and synthesis of small molecule inhibitors of the MDM2-p53 interaction as potential anti-tumor agents. Proc. Am. Assoc. Cancer Res. 40:1999;4099
12. ®, a high-density miniaturized thermal shift screening assay. Proc. Am. Assoc. Cancer Res. 44:2003;4584
13. Lu T., et al. Preparation of substituted 1, 4-benzodiazepinediones as MDM2 oncoprotein inhibitors for the treatment of cancer. PCT Int. Pat. Appl. Publ. WO 2003041715. 2003;3
14. Stoll R., et al. Chalcone derivatives antagonize interactions between the human oncoprotein MDM2 and p53. Biochemistry. 40:2001;336-344
15. Zhao J., et al. The initial evaluation of non-peptidic small-molecule HDM2 inhibitors based on p53-HDM2 complex structure. Cancer Lett. 183:2002;69-77
16. Zheleva D., et al. Bisarylsulfonamides - novel small molecule inhibitors of p53-Mdm2 interaction. Proc. Am. Assoc. Cancer Res. 45:2004;5552
17. Wang, S., et al. (2004) Bisarylsulfonamide compounds and their use in cancer therapy. PCT Int. Pat. Appl. Publ. WO 2004005278, Cyclacel Limited, UK.
18. Vassilev L.T., et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 303:2004;844-848
19. Zhang Z., et al. Antisense therapy targeting MDM2 oncogene in prostate cancer: effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc. Natl. Acad. Sci. U. S. A. 100:2003;11636-11641
20. Lane D.P., Fischer P.M. Turning the key on p53. Nature. 427:2004;789-790
21. Toogood P.L. Inhibition of protein-protein association by small molecules: approaches and progress. J. Med. Chem. 45:2002;1543-1558
22. Gadek T.R., Nicholas J.B. Small molecule antagonists of proteins. Biochem. Pharmacol. 65:2003;1-8
23. Bogan A.A., Thorn K.S. Anatomy of hot spots in protein interfaces. J. Mol. Biol. 280:1998;1-9
24. Lipinski C.A., et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46:2001;3-26
25. Veber D.F., et al. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45:2002;2615-2623