Ubiquitin-based drug discovery, such as Protein Targeting Chimeras (PROTAC) is at the exciting initial stages. PROTAC drugs are, hetero-bifunctional small molecules that bind at one end to an E3 ligase and at the other end to a protein meant to be degraded for therapeutic effect, has added a new dimension to proteostasis-based therapy. PROTACs have several advantages over simple DUB or E3 inhibitors or activators, including catalytic mechanism of action, reduced susceptibility to resistance owing to target mutation, and pharmacologic activity at concentrations lower than those usually needed for simple enzyme effectors. Progenra is developing a new class of PROTAC molecules that have demonstrated cell proof of concept and are now in the preclinical development stage. The drug discovery platform is complemented by internal biochemical, biological target validation programs and medicinal chemistry/lead optimization.