Selective, reversible and highly potent inhibitor of the USP1–UAF1 deubiquitinase complex that links deubiquitination to DNA damage responses (IC50 values of 76 nM in a ubiquitin-rhodamine (Ub-Rho) assay and 174 nM and 820 nM in orthogonal gel-based assays using K63-linked diubiquitin (di-Ub) and monoubiquitinated PCNA (Ub-PCNA) as substrates, respectively). ML323 effectively sensitized cisplatin-resistant NSCLC H596 cells and U2OS osteosarcoma cells to cisplatin since it simultaneously targets two major DNA damage response pathways (TLS and FA) by inhibiting a common deubiquitinase.

KEYWORDS: ML 323 | USP1-UAF1 inhibitor | ML323 |CAS[1572414-83-5] | Ubiquitin peptides | Deubiquitinase | Inhibitor | DNA damage |  cisplatin-resistant | TLS | FA