ML323 induces viral replication in vitro and in vivo. It may act as a potential candidate for the intervention of diseases like rheumatoid arthritis and systemic lupus erythematosus.
ML323 is a potent selective inhibitor of the USP1–UAF1 deubiquitinase complex with an IC50 of 76 nM in a ubiquitin-rhodamine (Ub-Rho) assay and excellent selectivity against other human deubiquitinases (DUBs), deSUMOylase, deneddylase and unrelated proteases. Human ubiquitin-specific protease 1 (USP1) associated with UAF1 is involved in the DNA damage response in the DNA translesion synthesis and Fanconi anemia pathways as the DUB responsible for deubiquitinating PCNA, which allows DNA replication past DNA lesions, and FANCD2 and FANCI, which function in interstrand crosslink repair. ML323 was found to potentiate cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells.