USP1 inhibitor TNG348

An orally bioavailable small molecule inhibitor of the human deubiquitinating enzyme ubiquitin specific protease 1 (USP1), with potential antineoplastic activity. Upon oral administration, USP1 inhibitor TNG348 specifically targets, allosterically binds to and inhibits the activity of USP1, thereby blocking USP1-mediated deubiquitinating activity. This may result in replication fork degradation, inhibition of DNA damage repair, and decreased tumor cell survival. USP1, a deubiquitinating enzyme overexpressed in various tumor cell types, plays a key role in the correct folding and deubiquitylation of proteins and facilitates DNA repair via its role regulating the Fanconi anemia complex and translesion synthesis. It plays a key role in the proliferation and survival of homologous recombination deficient (HRD)-positive tumor cells.