USP7-IN-18
USP7-IN-18 is a naphthalene derivative. USP7-IN-18 is a selective USP7 inhibitor (IC50 : 130.9 nM), with no or very weak inhibition of the other 8 DUBs including USP47. USP7-IN-18 specifically binds to the catalytic domain of USP7, blocking its deubiquitinase activity. USP7-IN-18 causes degradation of the oncogenic proteins MDM2 and DNMT1, and also degrades the novel target PCLAF. USP7-IN-18 activates the p53-p21 pathway. USP7-IN-18 exerts anti-tumor effects in colon cancer animal models and reshapes the tumor immune microenvironment. USP7-IN-18 achieves both direct cytotoxic and immune-synergistic anti-tumor actions.
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- CAS No.: 3052223-40-9
- Formule: C30H28ClN3O3S
- Masse moléculaire:546.08
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
USP7-IN-18 (Compound X21) (1.95-2000 nM, 3 min) binds to the catalytic domain of USP7 with a KD value of 4.9 μM, as determined by SPR analysis[1].
USP7-IN-18 (0.25-1 μM, 24 h) acts as a novel USP7 inhibitor by directly inhibiting enzymatic activity and regulating downstream pathways, including the first-reported target PCLAF[1].
USP7-IN-18 (0.01-100 μM, 72 h) significantly inhibits proliferation of leukemia (RS4;11) and colon cancer (MC38/CT26.WT) cells[1].
USP7-IN-18 (2.5 μM, 0.5 h) exhibits high selectivity for USP7 over eight other deubiquitinases, including USP47 (the most homologous to USP7)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RS4; 11 cells, MC38 cells, CT26.WT cells
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Concentration:0.01-100 μM in RS4; 11 cells, 0.5-100 μM in MC38 cells and CT26.WT cells
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Incubation Time:72 h
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Result:Demonstrated antiproliferative activity against the human leukemia RS4; 11 cell line with an IC50 value of 0.65 μM.
Exhibited antiproliferative activity against MC38 and CT26.WT mouse colon cancer cell lines with IC50 values of 2.93 μM and 2.89 μM, respectively.
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Cell Line:RS4; 11 cells
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Concentration:0.25 μM, 0.5 μM, 1 μM
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Incubation Time:24 h
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Result:Demonstrated downregulation of DNMT1, UHRF1, MDM2, TRIM27, and PCLAF, with concurrent upregulation of p53 and p21.
Significantly reduced PCLAF protein levels.
Slightly reduced USP7 protein levels.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:MC38 tumor-bearing C57BL/6J female mice (8 weeks)[1].
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Dosage:5 mg/kg, 10 mg/kg
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Administration:Daily intraperitoneal injection (i.p.), at the corresponding doses for 16 days.
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Result:Demonstrated significant tumor growth inhibition (TGI = 58.2%) at 10 mg/kg on day 16, while showing weaker efficacy at 5 mg/kg, indicating dose-dependent antitumor activity.
Significantly reduced tumor mass in immunocompetent mice, confirming effective tumor growth suppression.
Caused transient body weight loss due to initial stress response, with subsequent recovery observed in later stages.
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Animal Model:MC38 tumor-bearing BALB/c female mice (8 weeks)[1].
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Dosage:10 mg/kg
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Administration:Daily intraperitoneal injection (i.p.), at the corresponding doses for 16 days.
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Result:Demonstrated 19.24% tumor growth inhibition (TGI) without statistical significance and caused no body weight changes in mice.
Exhibited significantly attenuated antitumor efficacy in immunodeficient mice, suggesting immune microenvironment-dependent therapeutic activity.
Demonstrated significantly increased proportions of CD8+ T cells and elevated CD8+/CD4+ ratios, while exhibiting upward trends in NK cell proportions with unchanged Tregs/MDSCs ratios, collectively indicating tumor immune microenvironment remodeling.
Chemical Information
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CAS No. 3052223-40-9
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Masse moléculaire 546.08
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Formule C30H28ClN3O3S
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SMILES
CC1(C2C(N(C(C21)=O)CC3=CC4=C(C(C5=CC(Cl)=C6C=CC=CC6=C5OC7CCNCC7)=CC=N4)S3)=O)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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