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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C23H24N6 |
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分子量 | 384.48 | CAS No. | 1572414-83-5 | |
Solubility (25°C)* | 体外 | DMSO | 76 mg/mL (197.66 mM) | |
Ethanol | 38 mg/mL (98.83 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | ML323 displays reversible, nanomolar inhibitory activity and excellent selectivity toward USP1/UAF1 with IC50 of 76 nM. |
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in vitro | ML323 inhibits the deubiquitination of PCNA and FANCD2 by inhibiting USP1–UAF1 activity in H596 cells. Moreover, ML323 potentiates cisplatin cytotoxicity in NSCLC H596 cells and U2OS osteosarcoma cells by targeting two major DNA damage response pathways (TLS and FA). [1] |
in vivo | ML323 is a selective USP1–UAF1 inhibitor that inhibit deubiquitinase activity of USP1–UAF1 complex. |
特徴 | USP1-UAF1-selective inhibitor. |
キナーゼアッセイ | High-throughput screening | |
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For HTS, USP1-UAF1 activity is monitored using ubiquitin-rhodamine 110 as a substrate, where hydrolysis of the amide bond between the C-terminal glycine of ubiquitin and rhodamine results in an increase in fluorescence. The assay is miniaturized to a 4 μL volume in a 1,536-well format and is used to screen approximately 402,701 compounds in quantitative HTS mode, with each compound tested over a range of four to five concentrations. The assay shows robust performance with an average Z’factor of 0.8 throughout the screen. | ||
細胞アッセイ | 細胞株 | H596 cells |
濃度 | ~30 μM | |
反応時間 | 7-12 days | |
実験の流れ | For the colony-forming assay, cells are seeded at a density of 300–500 cells per well in six-well plates and grown overnight. Cells are then treated with ML323 alone, cisplatin alone or a combination of cisplatin and ML323 (1:1 or 1:4) at the indicated concentrations. Cells treated with an equal volume of DMSO and saline are used as control. After 48 h of treatment, fresh growth medium is added, and cells are incubated for an additional 5-10 d to allow for colony formation. For UV combination treatment, the cells are treated with ML323 at the indicated concentrations or an equal volume of DMSO. After 48 h, the medium is removed, and cells are irradiated at 254 nm at the indicated dosage. Fresh growth medium is added, and the cells are incubated for an additional 5-10 d to allow for colony formation. The cells without UV irradiation but treated with ML323 or an equal volume of DMSO are used as controls and designated as 100%. After the formation of the colonies, cells are fixed with methanol and stained with 0.5% crystal violet. Colonies consisting of >50 cells are scored. The number of colonies is determined from triplicate plates. The dose-response curves are generated using GraphPad Prism and analyzed by using CalcuSyn to calculate the combination index, which is determined for the fraction of cells affected after the addition of fixed ratios of cisplatin and the USP1-UAF1 inhibitor. |
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動物実験 | 動物モデル | Female C57BL/6J mice |
投薬量 | 10 mg/kg | |
投与方法 | i.p. |
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USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis [ Blood Adv, 2023, 7(13):3099-3112] | PubMed: 36912760 |
PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity [ PLoS One, 2023, 18(5):e0285337] | PubMed: 37205694 |
USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells [ J Exp Clin Cancer Res, 2021, 40(1):201] | PubMed: 34154657 |
A new role of GRP75-USP1-SIX1 protein complex in driving prostate cancer progression and castration resistance [ Oncogene, 2021, 40(25):4291-4306] | PubMed: 34079090 |
Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization [ Front Pharmacol, 2021, 12:695009] | PubMed: 34149436 |
USP1-WDR48 deubiquitinase complex enhances TGF-β induced epithelial-mesenchymal transition of TNBC cells via stabilizing TAK1 [ Cell Cycle, 2021, 1-12] | PubMed: 33461373 |
UAF1 deubiquitinase complexes facilitate NLRP3 inflammasome activation by promoting NLRP3 expression [ Nat Commun, 2020, 11(1):6042] | PubMed: 33247121 |
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143] | PubMed: 33067904 |
Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy. [ Cancer Sci, 2020, 10.1111] | PubMed: 32133742 |
USP1 inhibition destabilizes KPNA2 and suppresses breast cancer metastasis [ Oncogene, 2019, 38(13):2405-2419] | PubMed: 30531833 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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