The Myc transcription factor is a master regulator of cell growth and proliferation, and its dysregulation is a major driver of various cancers. However, Myc has earned the infamous honor of being an “undruggable” target, that of having compelling biology yet being refractory to potential therapeutic intervention by inhibition. Literature reports have shown that Omomyc, a 90 amino acid abridged form of Myc, can be used as a tool compound to restore homeostasis of the Myc pathway in various cancer models. Here we will detail our efforts to truncate the Omomyc polypeptide to improve its therapeutic potential as well as to create a more synthetically tractable molecule. We have shown much of Omomyc serves to fold and align the domains that interact with DNA, and that synthetic covalent templates can recapitulate this activity with correct presentation of the helical DNA binding domains. SAR of these artificial constructs, PK modulation and biological rationale will be discussed.

Abridged versions of the Myc transcription factor as potential Myc down-regulators

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.