USP1 - UAF1 inhibitor / Potent and reversible USP1-UAF1 deubiquitinase complex inhibitor with excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases, IC50=76 nm in a ubiquitin-rhodamine 110 assay.1 In H1299 non-small cell lung cancer cells treatment with ML323 dose dependently and robustly increased levels of monoubiquitinated PCNA compared to untreated cells at concentrations as low as 1 uM.1 It potentiates cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells.2 ML323 inhibition of upregulated USP1 in BRCA1-deficient tumor cells results in replication fork destabilization and decreased viability.3
Biochemicals & reagents
1572414-83-5
CID 60167849; NCGC00262306
1) Dexheimer et al. (2014), Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer; J. Med. Chem., 57 8099 2) Liang et al. (2014), A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses; Nat. Chem. Biol., 10 298 3) Lim et al. (2018) USP1 is required for replication fork protection in BRCA1-deficient tumors; Mol. Cell 72 925
-20°C
TARGET: DUB (Deubiquitinating enzyme) -- PATHWAY: Degradation -- RESEARCH AREA: Ubiquitin/Proteasome -- DISEASE AREA: Cancer