SHY-ONC6

SHY-ONC6 is a first-in-class, selective inhibitor of a subset of AAA+ ATPases in the 19S regulatory proteasome particle. The 19S regulatory particle is responsible for recognizing, binding, deubiquitinating, and unfolding proteins before their degradation by the 20S proteasome core. By inhibiting this process, SHY-ONC6 disrupts protein homeostasis and induces apoptosis in cancer cells. Preclinical studies show that SHY-ONC6 has significant activity against a broad range of human solid and hematologic tumor cell lines (IC50 ≤100 nM in ~80% of 869 tested lines) and demonstrates robust oral efficacy with tumor regression in multiple mouse xenograft models (including colon, gastric, lung [mesothelioma, small cell and non-small cell], myeloma, and pancreatic cancers). The compound also crosses the blood-brain barrier and has shown favorable pharmacokinetics as well as good tolerability in animal studies. It is being developed by SHY Therapeutics as an oncology therapeutic candidate[1].