USP1-IN-20
USP1-IN-20 is an orally effective and selective USP1 inhibitor with an IC50 of 3.0 nM. USP1-IN-20 inhibits the USP1-UAF1 complex, leading to the accumulation of Ub-PCNA, which in turn induces DNA damage and G2/M phase arrest, while simultaneously promoting the degradation of the oncogenic protein c-MYC. USP1-IN-20 can be used for research on breast cancer and diffuse large B-cell lymphoma.
For research use only. We do not sell to patients.
- CAS No.: 3094127-54-2
- Formula: C28H25F3N6O
- Molecular Weight:518.53
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Storage:
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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Biological Activity
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Biological Activity
Description
IC50 & Target
[1]|
USP1 3.0 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-436 | GI50 |
16.2 nM
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Antiproliferative activity against BRCA1-mutant triple-negative breast cancer MDA-MB-436 cells assessed as inhibition of cell growth.
Antiproliferative activity against BRCA1-mutant triple-negative breast cancer MDA-MB-436 cells assessed as inhibition of cell growth.
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acs.jmedchem.6c01009 |
| MDA-MB-436 | IC50 |
11.5 nM
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Inhibition of colony formation in BRCA1-deficient MDA-MB-436 cells.
Inhibition of colony formation in BRCA1-deficient MDA-MB-436 cells.
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acs.jmedchem.6c01009 |
In Vitro
USP1-IN-20 (compound 38 a) (7 days) selectively inhibits the proliferation of BRCA-deficient cancer cells, especially MDA-MB-436 cells, with a GI50 of 16.2 nM, while having little effect on BRCA wild-type and normal cells[1].
USP1-IN-20 (10 nM-10 μM; 10 days) exhibits significant colony formation inhibitory activity in MDA-MB-436 cells with an IC50 of 11.5 nM[1].
USP1-IN-20 (30 nM-1 μM; 24 h) induces G2/M cell cycle arrest, causes significant accumulation of Ub-PCNA and γ-H2AX protein levels, and leads to downregulation of c-MYC protein levels in MDA-MB-436 cells[1].
USP1-IN-20 (15 min) exhibits extremely potent USP1-UAF1 inhibitory activity in the USP1 enzymatic assay, with an IC50 of 3.0 nM[1].
USP1-IN-20 (1 μM) showed weak inhibition of Src kinase in a 120-kinase selectivity screen, with no significant activity against other kinases[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:30, 300, 1000 nM
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Incubation Time:24 h
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Result:Dose-dependently induced significant G2/M phase cell cycle arrest (arrest rate increased from 19.4% to 34.3%).
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Cell Line:MDA-MB-436 cells
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Concentration:30, 100, 300, 1000 nM
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Incubation Time:24 h
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Result:Induced a dose-dependent accumulation of Ub-PCNA and the DNA damage marker γ-H2AX, and significantly down-regulated c-MYC protein levels.
Parmacokinetics
In Vivo
USP1-IN-20 (100 mg/kg; oral administration; once daily; 27 days) significantly inhibited tumor growth in a DLBCL-derived xenograft NOD-SCID mouse model with high c-MYC expression and TP53 mutation, with efficacy comparable to the first-line standard therapy R-CHOP[1].
USP1-IN-20 (100-300 mg/kg; oral administration; once daily; 4 weeks) had mild and reversible immunomodulatory side effects and abnormal liver enzyme effects in normal BALB/c mice, without long-term irreversible organ structural damage[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:50 mg/kg, 100 mg/kg
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Administration:p.o.; once daily; 34 days
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Result:Induced dose-dependent tumor growth inhibition with TGI rates of 4.5% at 50 mg/kg and 33.6% at 100 mg/kg.
Upregulated Ub-PCNA, significantly elevated P27 and P21 levels, and accumulated γ-H2AX in all treated groups.
Induced no significant body weight loss.
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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.; once daily; 27 days
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Result:Suppressed tumor growth with a TGI rate of 64.7%.
Maintained stable or increased body weight over the treatment period.
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Animal Model:Mice[1]
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Dosage:100 mg/kg, 300 mg/kg
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Administration:p.o.; once daily; 4 weeks
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Result:Induced no significant changes in body weight at both doses.
Induced significant abnormalities in hepatic function markers (ALP, ALT, AST) after 4 weeks, which mostly normalized within 2 weeks of dosing cessation.
Revealed no overt structural damage to the liver or other organs via H&E staining.
Chemical Information
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CAS No. 3094127-54-2
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Molecular Weight 518.53
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Formula C28H25F3N6O
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SMILES
CN1C(C2=CC=C(CN3C4=CC(C5=C(N=CN=C5OC)C6CC6)=NC(C)=C4C=C3)C=C2)=NC(C(F)(F)F)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
USP1-IN-20 Related Classifications
HY-189455 Related Classifications
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