Discovery of a MAX Binder That Modulates c-MYC Activity in Cancer
The transcription factor c-MYC is a promising, but challenging target deregulated in ~70% of human cancers. We utilized high-throughput screens to identify KI-MS2 as a small molecule binder of MAX, the obligate protein partner of c-MYC. In cells, KI-MS2 treatment modulated c-MYC transcriptional activity, inhibited cell viability in a c-MYC-dependent manner, and mimicked c-MYC inactivation. Additionally, KI-MS2 suppressed the growth of c-MYC-driven tumors in mouse models.