发明名称 |
PHARMACOLOGIC INHIBITION OF MYC FUNCTION |
摘要 |
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. |
申请公布号 |
WO03105759(A3) |
申请公布日期 |
2004.03.04 |
申请号 |
WO2003US18537 |
申请日期 |
2003.06.12 |
申请人 |
UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION |
发明人 |
PROCHOWNIK, EDWARD, V.;GIAP, CHRISTINE;LAZO, JOHN, S.;YIN, XIAOYING |
分类号 |
A61K31/135;A61K31/137;A61K31/41;A61K31/4245;A61K31/425;A61K31/427;A61K31/445 |
主分类号 |
A61K31/135 |
代理机构 |
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