C-MYC amplifications, translocations, and rearrangements are frequently observed in cancer. Elevated expression of the proto-oncogene c-MYC in cancer cells promotes tumorigenesis and metastasis by enacting broad transcriptional changes in genes that regulate cellular processes such as proliferation, metabolism and cell survival.

Junying Yuan’s lab at Harvard Medical School has developed small molecule inhibitors that block the E3 ubiquitin ligase responsible for ubiquitination and degradation of MAD, a c-MYC antagonist and crucial player in c-MYC’s cancer cell growth-promoting effects. The drugs’ mechanism of action is to therefore inhibit the breakdown of MAD and subsequent activation of c-MYC. The compounds exhibit effective antitumor activity both in cells and in xenograft mouse models, demonstrating their therapeutic potential.