Definition

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 ISM3091 specifically targets, 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.