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| Product Name: | ML-323 | | Synonyms: | ML-323;5-Methyl-2-[2-(1-methylethyl)phenyl]-N-[[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl]-4-pyrimidinamine;4-Pyrimidinamine, 5-methyl-2-[2-(1-methylethyl)phenyl]-N-[[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl]-;5-Methyl-2-[2-(1-methylethyl)phenyl]-N-[[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl]-4-pyrimidinamine ML323;ML323, >=98%;N-(4-(1H-1,2,3-Triazol-1-yl)benzyl)-2-(2-isopropylphenyl)-5-methylpyrimidin-4-amine;ML323, 99%, an USP1-UAF1 inhibitor;5-Methyl-2-(2-propan-2-ylphenyl)-N-[[4-(triazol-1-yl)phenyl]methyl]pyrimidin-4-amine | | CAS: | 1572414-83-5 | | MF: | C23H24N6 | | MW: | 384.48 | | EINECS: | | | Product Categories: | Inhibitors | | Mol File: | 1572414-83-5.mol |  |
| | ML-323 Chemical Properties |
| Boiling point | 515.4±60.0 °C(Predicted) | | density | 1.20±0.1 g/cm3(Predicted) | | storage temp. | -20°C | | solubility | Soluble in DMSO (up to 40 mg/ml), or in Ethanol (up to 20 mg/ml) | | pka | 5.37±0.10(Predicted) | | form | solid | | color | White | | Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. |
| | ML-323 Usage And Synthesis |
| Description | ML323 (1571424-83-5) is a 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 μM.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 | | Uses | ML323 is a highly potent and selective USP1-UAF1 inhibitor. | | in vitro | studies in h596 cells showed that ml-323 blocked the deubiquitination of pcna and fancd2 via suppressing usp1–uaf1 activity. it was reported that ml-323 potently inhibited usp1-uaf1 with ic50 values of 76 nm and 174 nm in ubiquitin-rhodamine (ub-rho) assay and orthogonal gel-based assay, respectively. in addition, by targeting tls and fa, two major dna damage response pathways, ml-323 increased cisplatin cytotoxicity both in nsclc h596 cells and u2os osteosarcoma cells. moreover, this agent exhibited a high selectivity to human dubs, desumoylase, deneddylase and unrelated proteases. [1] | | target | USP1-UAF1 | | IC 50 | ml-323 is a highly potent and selective inhibitor of usp1-uaf1 with ic50 value of 76 nm. | | storage | Store at -20°C | | References | 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 |
| | ML-323 Preparation Products And Raw materials |
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