CST, 77681S, ML-323

Chemical Modulators for studying in the research area. Product Usage Information ML-323 is supplied as a lyophilized powder. For a 15 mM stock, reconstitute 5 mg of powder in 0.87 mL of DMSO. Working concentrations and length of treatment can vary depending on the desired effect. Storage Store lyophilized at -20ºC, desiccated. In lyophilized form, the chemical is stable for 24 months. Once in solution, store at -20ºC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles . Background ML-323 is a small-molecule inhibitor of ubiquitin-specific protease 1 (USP1), a deubiquitinase associated with the DNA damage response. USP1 and the WD repeat-containing protein (WDR48, UAF1) form a deubiquitinase complex that removes ubiquitin from FANCD2, which is ubiquitinated in response to DNA damage. ML-323 is a potent (IC = 76 nM) and specific inhibitor of the USP1/UAF1 deubiquitinase complex (1). Dysregulation of USP1 is an aspect of several forms of cancer, making it a promising therapeutic target. ML-323 significantly repressed metastasis in a murine model of breast cancer (2) and decreased hepatocellular carcinoma cell proliferation (3). Elevated USP1 expression in some colorectal cancers is associated with short overall patient survival and advanced stages of cancers. USP1 knockdown resulted in growth arrest at G2/M and reduced anti-apoptotic protein expression; ML-323 sensitized colorectal cancer cells to DNA-targeting chemotherapeutics (4). ML-323 treatment of non-small cell lung cancer and osteosarcoma cells potentiates the cytotoxic effects of cisplatin (5). Alternate Names CID 60167849; N-(4-(1H-1,2,3-Triazol-1-yl(benzyl)-5-methyl-2-(2-isopropylphenyl)pyrimidin-4-amine; NCGC00262306-01