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Small Molecule Inhibitors of Myc for Cancer Therapeutics

Detailed Technology Description
None
*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.Non exclusive license available
*Principal Investigator

Name: Christine Giap

Department:


Name: John Lazo, Professor Emeritus

Department: Departments of Pharmacology & Chemistry


Name: Edward Prochownik

Department: Med-Pediatrics


Name: Xiaoying Yin

Department:

Country/Region
USA

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