ERG degrader

Disease Need

ERG overexpression occurs in approximately 40% of all prostate cancer patients due to the formation of a chromosomal fusion between TMPRSS2 and ERG genes. This fusion is an N-terminal deleted mutant that promotes oncogenicity of prostate tumors. Targeting the ERG protein in prostate tumors is intended to provide a novel therapeutic option for patients with castrate-resistant prostate cancer.

Our Approach

The ERG degrader uses Helicon™ technology to bind to one of the most unique regions of the ERG protein and employs an E3 ligand to target the ERG protein for degradation through the ubiquitin-proteosome system. The goal is to specifically reduce ERG protein levels without targeting structurally similar ETS-transcription factor family members. Degrading ERG prevents all of its biological functions which include activating transcription of certain genes, interfering with androgen receptor activity, and altering chromatin accessibility and structure. It is believed that all of these functions play a role in the oncogenicity of ERG, and thus ERG degradation should provide the strongest anti-tumor activity.