ERG-degrading Helicon peptides

ERG-degrading Helicon peptides are stabilized α-helical bifunctional peptides engineered to directly bind the ETS transcription factor ERG and recruit an E3 ubiquitin ligase, resulting in targeted degradation of ERG via the ubiquitin-proteasome pathway. They are designed specifically to address the TMPRSS2–ERG fusion subtype of prostate cancer, found in 40-50% of cases, and have shown potent, selective degradation of ERG protein in vitro and in vivo with resultant downregulation of Myc target genes and substantial tumor growth inhibition in preclinical xenograft models. These peptide degraders are derived from Parabilis Medicines’ Helicon discovery platform, optimized for potency, selectivity, and favorable pharmacokinetics, and represent a first-in-class approach to pharmacologically validate ERG as a dependency in ERG-fusion-positive prostate cancer, a target previously considered undruggable with small molecules. They are in late-stage lead optimization with IND-enabling studies anticipated.

Other names

Helicon peptide degraderHelicon ERG degraderERG Helicon degrader