Pharmacologic inhibition of Myc function

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C514S150000, C514S364000, C514S369000, C514S424000, C514S654000

Reexamination Certificate

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07026343

ABSTRACT:
The c-Myc oncoprotein, a helix-loop-helix-leucine zipper (HLH-ZIP) transcription factor, is frequently deregulated in human cancers. All known functions of c-Myc, including those pertaining to transformation, require that it heterodimerize with another HLH-ZIP protein, Max. Using a high throughput yeast-based assay, we identified seven low molecular weight substances that inhibit c-Myc-Max association. Each compound also prevented this interaction in vitro and inhibited the growth of c-Myc-expressing fibroblasts, although not of fibroblasts lacking c-Myc. Finally, short-term exposure of c-Myc over expressing fibroblasts to several of the compounds markedly reduced their in vivo tumorigenicity. These studies suggest that yeast-based assays can be used to identify inhibitors of protein-protein interactions and that these frequently function in mammalian cells. The signature specificities of each of the c-Myc-Max compounds identified here further suggest synergistic in vivo function.

REFERENCES:
Nupponen, Nina N., Kakkola, Laura, Koivisto, Pasi and Visakorpi, Tapio, “Genetic Alterations in Hormone-Refractory Recurrent Prostate Carcinomas,”American Journal of Pathology, vol. 153, No. 1, pp. 141-148 (Jul. 1998).
Langlands, Kenneth and Prochownik, Edward V., “A Rapid Method for the Preparation of Yeast Lysates That Facilitates the Immunodetection of Proteins Generated by the Yeast Two-Hybrid System,”Analytical Biochemistry, vol. 249, pp. 250-252 (1997).
Bazarov, Alex V., et al., “A Modest Reduction in c-Myc Expression Has Minimal Effects on Cell Growth and Apoptosis But Dramatically Reduces Susceptibility to Ras and Raf Transformation,”Cancer Research, vol. 61, pp. 1178-1186 (Feb. 1, 2001).
Yin, Xiao-Ying, et al., “Inverse Regulation of Cyclin B1 by c-Myc and p53 and Induction of Tetraploidy by Cyclin B1 Overexpression,”Cancer Research, vol. 61, pp. 6487-6493 (Sep. 1, 2001).
Jenkins, Robert B., Qian, Junqi, Lieber, Michael M. and Bostwick, David G., “Detection of c-myc Oncogene Amplification and Chromosomal Anomalies in Matastatic Prostatic Carcinoma by Fluorescence in Situ Hybridization,”Cancer Research, vol. 57, pp. 524-531 (Feb. 1, 1997).
Kimura, Shinya, Maekawa, Taira, Hirakawa, Kouichi, Murakami, Akira and Abe, Tatsuo, “Alterations of c-myc Expression by Antisense Oligodeoxynucleotides Enhance the Induction of Apoptosis in HL-60 Cells,”Cancer Research, vol. 55, pp. 1379-1384 (Mar. 15, 1995).
Nesbit, Chadd E., Grove, Linette E., Yin, Xiaoying and Prochownik, Edward V., “Differential Apoptotic Behaviors of c-myc, N-myc, and L-myc Oncoproteins,”Cell Growth&Differentiation, vol. 9, pp. 731-741, (Sep. 1998).
Mateyak, Maria K., Obaya, Alvaro J., Susumu and Sedivy, John M., “Phenotypes of c-Myc-Deficient Rat Fibroblasts Isolated by Targeted Homologous Recombination,”Cell Growth&Differentiation, vol. 8, pp. 1039-1048 (Oct. 1997).
Bowlin, Terry L., McKown, Brenda J. and Sunkara Prasad S., “Omithine Decarboxylase Induction and Polyamine Biosynthesis Are Required for the Growth of Interleukin-2- and Interleukin-3-Dependent Cell Lines,”Cellular Immunology, vol. 98, pp. 341-350 (1986).
Prochownik, Edward V., Grove, Linette Eagle, Deubler, Debra, et al., “Commonly Occuring Loss and Mutation of the MXI1 Gene in Prostate Cancer,”Genes, Chromosomes&Cancer, vol. 22, pp. 295-304 (1998).
Davis, Ann C., Wims, Marie, Spotts, Gerald D., Hann, Stephen R. and Bradley, Allan, “A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice,”Genes&Development, vol. 7, pp. 671-682 (1993).
Shapiro, David N., Valentine, Virginia, Eagle, Linette, et al., “Assignment of the Human MAD and MXI1 Genes to Chromosomes 2p12-p13 and 10q24-q25,”Genomics, vol. 23, pp. 282-286 (1994).
Steiner, Mitchell S., Anthony, Catherine T., Lu, Yi and Holt, Jeffrey T., “Antisense c-myc Retroviral Vector Suppresses Established Human Prostate Cancer,”Human Gene Therapy, vol. 9, pp. 747-755 (Mar. 20, 1998).
Ge, Kai, Minhas, Farooq, Duhadaway, James, Mao, Nien-Chen, et al., “Loss of Heterozygosity and Tumor Suppressor Activity of BIN1 in Prostate Carcinoma,”Int. J. Cancer, vol. 86, pp. 155-161, (2000).
Van Waardenburg, Robert C.A.M., Meijer, Coby, et al., “Effects of an Inducible Anti-Sense c-myc Gene Transfer in a Drug-Resistant Human Small-Cell Lung-Carcinoma Cell Line,”Int. J. Cancer, vol. 73, pp. 544-550 (1997).
Yin, Xiaoying, Grove, Linnette, et al., “Myc Target in Myeloid Cells-1, a Novel c-Myc Target, Recapitulates Multiple c-Myc Phenotypes,”The Journal of Biological Chemistry, vol. 277, No. 22, pp. 19998-20010, (May 31, 2002).
Langlands, Kenneth, Yin, Xiaoying, et al., “Differential Interactions of Id Proteins with Basic-Helix-Loop-Helix Transcription Factors,”The Journal of Biological Chemistry, vol. 277, No. 32, pp. 19785-19793, (Aug. 8, 1997).
Zhang, Hong, Fan, Saijun and Prochownik, Edward V., “Distinct Roles of MAX Protein Isoforms in Proliferation and Apoptosis,”The Journal of Biological Chemistry, vol. 272, No. 28, pp. 17416-17424, (Jul. 11, 1997).
DuHadaway, James B., Lynch, Frank J., et al., “Immunohistochemical Analysis of Bin1/Amphiphysin II in Human Tissues: Diverse Sites of Nuclear Expression and Losses in Prostate Cancer,”Journal of Cellular Biochemistry, vol. 88, pp. 635-642 (2003).
Ebinuma, Hirotoshi, Saito, Hidetsugu, Kosuga, Motomichi, et al., “Reduction of c-myc Expression by an Antisense Approach under Cre/loxP Switching Induces Apoptosis in Human Liver Cancer Cells,”Journal of Cellular Physiology, vol. 188, pp. 56-66 (2001).
Bai, Chang and Elledge, Stephen J., “Gene Identification Using the Yeast Two-Hybrid System,”Methods in Enzymology, vol. 273, pp. 331-347 (1996).
Prochownik, Edward V., Kukowska, Jolanta and Rodgers, Claire, “c-myc Antisense Transcripts Accelerate Differentiation and Inhibit G1Progression in Murine Erythroleukemia Cells,”Molecular and Cellular Biology, vol. 8, No. 9, pp. 3683-3695 (Sep. 1998).
Smith, Michael J., Charron-Prochownik, Denise C., et al., “The Leucine Zipper of c-Myc is Required for Full Inhibition of Erythroleukemia Differentiation,”Molecular and Cellular Biology, vol. 10, No. 10, pp. 5333-5339 (Oct. 1990).
Freytag, Svend O., “Enforced Expression of the c-myc Oncogene Inhibits Cell Differentiation by Precluding Entry into a Distinct Predifferentiation State in G0/G1,”Molecular and Cellular Biology, vol. 8, No. 4, pp. 1614-1624 (Apr. 1998).
Schreiber-Agus, Nicole, Meng, Yong, Hoang, Tin, et al., “Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth,”Nature, vol. 393, pp. 483-487 (Jun. 4, 1998).
Auvinén, Merja, Paasineen, Aino, Andersson, Leif C. and Hölttä, Erkki, “Ornithine decarboxylase activity is critical for cell transformation,”Nature, vol. 360, pp. 355-358 (Nov. 26, 1992).
O'Hagan, Rónán C., Schriber-Agus, Nicole, Chen, Ken, et al., “Gene-target recognition among members of the Myc superfamily and implications for oncogenesis,”Nature Genetics, vol. 24, pp. 113-119 (Feb. 2000).
Eagle, Linette R., Yin, Xiaoying, Brothman, Arthur R., et al., “Mutation of the MXI1 gene in prostate cancer,”Nature Genetics, vol. 9, pp. 249-255 (Mar. 1995).
Landolfi, Nicholas F., Yin, Xiao-Ming, Capra, J. Donald and Tucker, Phillip W., “A conserved heptamer upstream of the IgH promoter region octamer can be the site of a coordinate protein—DNA interaction,”Nucleic Acids Research, vol. 16, No. 12, pp. 5503-5514 (1988).
Littlewood, Travor D., Hancock, David C., Danielian, Paul S., et al., “A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins,”Nucleic Acids Resear

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