USP1-IN-18
USP1-IN-18 is an orally active USP1 inhibitor with a human IC50 of 17.0 nM. USP1-IN-18 inhibits USP1-UAF1 deubiquitinase activity and drives ubiquitinated PCNA accumulation. USP1-IN-18 induces DNA damage, replication stress, and G2-M phase cell cycle arrest. USP1-IN-18 can be used for the research of triple-negative breast cancer.
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- CAS No.: 3064481-29-1
- 화학식: C26H22F3N7O2
- 분자량:521.49
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
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USP1 |
USP1-IN-18 (Compound 57) potently inhibits the purified USP1-UAF1 complex with an IC50 of 17 nM via stable binding to a hydrophobic tunnel and induction of a key β-turn conformational shift[1].
USP1-IN-18 (10-10000 nM; 24 h-12 days) inhibits MDA-MB-436 triple-negative breast cancer cell proliferation with an IC50 of 173 nM, induces G2-M phase arrest[1].
USP1-IN-18 exhibits favorable metabolic stability in human, monkey, rat, mouse, and dog liver microsomes, with a half-life >120 min and intrinsic clearance <12 mL/min/kg in human liver microsomes[1].
USP1-IN-18 (7 days) shows minimal cytotoxicity in nonmalignant LX-2, Vero, and H9C2 cell lines, with IC50 values >30 μM after 7 days of treatment[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 triple-negative breast cancer cells
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Concentration:10 nM; 30 nM; 100 nM; 300 nM; 1000 nM; 3000 nM; 10000 nM
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Incubation Time:12 days
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Result:Inhibited MDA-MB-436 cell proliferation with an IC50 of 173 nM.
Dose-dependently suppressed colony formation, with significant inhibition observed at concentrations ≥30 nM.
Induced G2-M phase arrest: at 300 nM, the proportion of cells in G2-M phase increased from 19.4% to 30.5%.
Caused dose-dependent accumulation of ubiquitinated PCNA after 4 h treatment, confirming USP1 inhibition.
Upregulated P27 protein levels after 24 h treatment.
Showed minimal inhibition of other tested USP family members at concentrations exceeding those required for USP1 inhibition, demonstrating target selectivity.
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Cell Line:MDA-MB-436 triple-negative breast cancer cells
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Concentration:30 nM; 300 nM; 1000 nM
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Incubation Time:24 h
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Result:Induced G2-M phase arrest.
USP1-IN-18 (100-300 mg/kg; p.o.; daily; 30 days) is well tolerated in female Balb/c mice at doses up to 300 mg/kg administered daily for 30 days, with no evident subacute toxicity[1].
USP1-IN-18 (400-800 mg/kg; p.o.; single dose) is well tolerated in female Balb/c mice at single oral doses up to 800 mg/kg, with no evident acute toxicity[1].
USP1-IN-18 (10 mg/kg; p.o.; single dose) exhibits favorable oral pharmacokinetic properties in rats, with 76% oral bioavailability following a single 10 mg/kg dose[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID mice[1]
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Dosage:100 mg/kg
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Administration:p.o.; daily; 34 consecutive days
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Result:Achieved a tumor growth inhibition (TGI) of 42%.
Markedly increased ubiquitinated PCNA (ub-PCNA) and γ-H2AX levels in xenograft tumor tissues.
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Animal Model:Balb/c mice (female, 6−8 weeks old, 18−22 g)[1]
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Dosage:100 mg/kg; 300 mg/kg
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Administration:p.o.; daily; 30 days
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Result:Caused no significant alterations in general health status, mortality, or body weight.
Revealed no organ damage via histopathological assessment (H&E staining).
Restored hematological parameters (neutrophils, lymphocytes) to normal after the 14-day drug-free period.
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Animal Model:Balb/c mice (female, 6−8 weeks old, 18−22 g)[1]
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Dosage:400 mg/kg; 600 mg/kg; 800 mg/kg
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Administration:p.o.; single dose
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Result:Caused no significant tissue damage or pathological alterations after the 14-day drug-free period.
Showed a slight increase in platelet (PLT) levels, but no statistically significant changes in other hematological or serum biochemical parameters.
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Animal Model:Sprague-Dawley rats[1]
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Dosage:10 mg/kg
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Administration:p.o.; single dose
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Result:Resulted in an area under the concentration-time curve (AUC0-t) of 1963.0 μg·h/L, an elimination half-life (T1/2) of 7.5 h, a maximum plasma concentration (Cmax) of 956.7 μg/L, and an oral bioavailability (F) of 76%.
Chemical Information
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CAS No. 3064481-29-1
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분자량 521.49
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화학식 C26H22F3N7O2
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SMILES
COC1=NC=NC(C2CC2)=C1C3=CC(N(CC4=CC=C(C5=NC(C(F)(F)F)=CN5C)C=C4)C(N6)=O)=C6C=N3
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
USP1-IN-18 Related Classifications
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