USP1-IN-15
USP1-IN-15 is an orally active and selective USP1 inhibitor with an IC50 of 12.3 nM. USP1-IN-15 has a high specificity for USP1 with negligible inhibition against all off-target DUBs. USP1-IN-15 suppresses colony formation, induces S-phase arrest, and stabilizes ubiquitinated PCNA. USP1-IN-15 also shows synergistic antiproliferative activity. USP1-IN-15 achieves significant tumor growth inhibition in vivo. USP1-IN-15 can be used for BRCA-mutated breast cancer.
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- Formule: C30H24F3N9O2
- Masse moléculaire:599.57
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
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Activité biologique
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USP1 12.3 nM (IC50) |
USP1-IN-15 (compound 43) (14 days) balances profile of potent antiproliferative activity with IC50 = 0.07 μM in MDA-MB-436 and good metabolic stability (t1/2 value exceeding 120 min) [1].
USP1-IN-15 (1 μM) has a high specificity for USP1 with negligible inhibition against all off-target DUBs (USP5, USP7, USP8, USP9X, USP14, USP15, USP25, USP28, BAP1, and OTUD1) [1].
USP1-IN-15 (0-1000 nM, 0-168 h) dose-and time-dependently potently and persistently inhibits the deubiquitination of proliferating cell nuclear antigen (PCNA) and induces protein level of p-H2AX in MDA-MB-436 breast cancer cells[1].
USP1-IN-15 (100-1000 nM, 48 h or 2-3 weeks) induces S-phase arrest in MDA-MB-436 breast cancer cells[1].
USP1-IN-15 (0.1-10 μM, 7 days or 2-3 weeks) dose dependently enhances growth inhibition compared to monotherapy when combined with Olaparib (HY-10162) in MDA-MB-436 cells[1].
USP1-IN-15 (1 μM, 48 h) has superior synergistic activity when combined with Olaparib through enhanced induction of DNA damage and cell cycle arrest in MDA-MB-436 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-436 cells
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Concentration:0.3, 1, 3, 10, 30, 100, 300 and 1000 nM
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Incubation Time:0, 6, 24, 48, 72, 96, 120, 144, and 168 h
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Result:Exhibited deubiquitination inhibition, increased the protein level of ubiquitinated PCNA (ubPCNA) and induced the protein level of p-H2AX0 at 48 h and beyond in range of 0-168 h and 300 nM.
Increased the protein level of ubPCNA in a dose-dependent manner at lower concentrations (100 and 300 nM) .
Showed significantly higher ubPCNA levels at 100, 300, and 1000 nM.
Elevated p-H2AX protein levels at 100, 300, and 1000 nM.
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Cell Line:MDA-MB-436 cells
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Concentration:300 nM
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Incubation Time:72 h
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Result:Induced the superior p-H2AX signal intensity and more nuclear foci.
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Cell Line:MDA-MB-436 cells
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Concentration:100, 300, 1000 nM
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Incubation Time:2-3 weeks
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Result:Inhibit the growth of clones in a dose-dependent manner.
Demonstrated superior antiproliferative activity, reducing colony counts by 55.99 % (300 nM) and 66.89% (1000 nM) .
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Cell Line:MDA-MB-436 cells
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Concentration:100, 300, 1000 nM
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Incubation Time:48 h
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Result:Induced S-phase arrest at a concentration range of 100-1000 nM.
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Cell Line:MDA-MB-436 cells
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Concentration:0.1, 1, 10 μM
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Incubation Time:7 days
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Result:Revealed stronger cell growth inhibition in combination regimens when combination with Olaparib.
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Cell Line:MDA-MB-436 cells
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Concentration:1 μM
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Incubation Time:48 h
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Result:Induced significant cell cycle arrest with marked accumulation of cells in the S phase but induced significant accumulation of MDA-MB-436 cells at S and G2/M phases when combined with Olaparib.
Exhibited pronounced synergistic effects, resulting in a more robust cell cycle perturbation when combined with Olaparib.
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Cell Line:MDA-MB-436 cells
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Concentration:1 μM
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Incubation Time:48 h
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Result:Elevated p-H2AX levels with or without combination with Olaparib but had a better effect when combinated with Olaparib.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:MDA-MB-436 cells (5 × 106) induced-female nude mice(6-9 weeks, 17-19 g)[1]
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Dosage:40 mg/kg
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Administration:p.o., once daily, for 45 days, with or without combination with Olaparib (30 mg/kg)
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Result:Exhibited the most potent antitumor activity.
Exhibiting the most significant reduction (TGI = 82.734%) in tumor weight.
Observed no significant differences in body weight.
Demonstrated no statistically significant differences in organ indices of heart, liver, lung, and kidney.
Resulted significant reductions in Ki67-positive cells in both monotherapy or combination groups.
Elevated levels of ubPCNA in monotherapy.
Exhibited the highest level of p-H2AX, consistent with its robust DNA damage-inducing capability.
Chemical Information
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Masse moléculaire 599.57
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Formule C30H24F3N9O2
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SMILES
O=C1C2=NC=CN2C3=CN=C(N=C3N1CC4=CC=C(C=C4)N5N=C(C=C5C6CC6)C(F)(F)F)C7=C(N=CN=C7C8CC8)OC
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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)
USP1-IN-15 Related Classifications
HY-180216 Related Classifications
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