TUS-007

TUS-007 is a first-in-class, orally active small molecule degrader designed to target and eliminate mutant KRAS proteins, specifically KRAS G12D and KRAS G12V. It was developed using the CANDDY (Chemical Knockdown Based on Conjugation of a Target Ligand with a Proteasome-Directing Tag) technology. Unlike traditional PROTACs (Proteolysis-Targeting Chimeras) that rely on the recruitment of E3 ubiquitin ligases to label targets for destruction, TUS-007 facilitates the direct recruitment of the target protein to the proteasome. This allows for ubiquitination-independent degradation, a mechanism that overcomes common resistance pathways associated with the ubiquitin-proteasome system. Preclinical studies have shown that TUS-007 can induce apoptosis and suppress tumor growth in models of cetuximab-resistant colorectal cancer and pancreatic carcinoma.