cMyc is a transcription factor that regulates expression of many growth-related target genes, and as such is involved in a variety of cellular functions including cell cycle progression, apoptosis, and maintenance of cell size, morphology, and genomic integrity. Due to the almost ubiquitous nature of cMyc genomic targets, its expression is tightly regulated at the transcriptional, translational, and posttranslational level. cMyc heterodimerization with Max is required for its association with DNA and stimulation of transcription.
cMyc is a proto-oncogene deregulated in many tumors, estimated at approximately 70% of all cancers. Upregulated cMyc gene expression or posttranslational modifications resulting in increased activation and/or decreased degradation are considered important drivers of oncogenesis. High cMyc expression is prognostic for unfavorable outcomes in renal, urothelial and ovarian cancers (p<0.001; The Human Protein Atlas). Due to its lack of enzymatic activity, it has historically been viewed as an “undruggable” cancer target. Disruption of the interaction of cMyc with Max, however, inhibits Myc-driven transcriptional programs to decrease tumor cell proliferation and induce cell death.
Sapience is targeting the interaction of cMyc with Max, a co-activator required for cMyc biological activity. Our cMyc-antagonist peptides are specific to the cMyc-Max interaction, and do not disrupt Max heteromeric interactions with MXD family proteins that function to negatively regulate cMyc activity. Cell-free experiments demonstrate target engagement, and initial in vitro data sets indicate potent inhibition of cMyc-dependent gene transactivation by reporter assay and significant cell kill against cMyc-dependent tumor cell lines.