2. Cell Cycle/DNA Damage
  3. Deubiquitinase DNA/RNA Synthesis
  4. 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.

For research use only. We do not sell to patients.

USP1-IN-18

USP1-IN-18 Chemical Structure

CAS No. : 3064481-29-1

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USP1-IN-18 Related Antibodies

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Description

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[1].

IC50 & Target[1]

USP1

 

In Vitro

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.

USP1-IN-18 Related Antibodies

Cell Proliferation Assay[1]

Cell Line: MDA-MB-436 triple-negative breast cancer cells
Concentration: 10 nM; 30 nM; 100 nM; 300 nM; 1000 nM; 3000 nM; 10000 nM
Incubation Time: 12 days
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.

Cell Cycle Analysis[1]

Cell Line: MDA-MB-436 triple-negative breast cancer cells
Concentration: 30 nM; 300 nM; 1000 nM
Incubation Time: 24 h
Result: Induced G2-M phase arrest.
Parmacokinetics
Species Dose Route AUC0-t T1/2 Tmax Cmax MRT0-t Vz CLz/F F
Rat[1] 10 mg/kg i.v. 2598300 μg·h/mL 5.7 h 0.08 h 1598.5 μg/L 3.2 h 33.9 L/kg 4.6 L/h/kg /
Rat[1] 10 mg/kg p.o. 1963000 μg·h/mL 7.5 h 0.33 h 956.7 μg/L 5.2 h 49.9 L/kg 4.8 L/h/kg 76 %
In Vivo

USP1-IN-18 (Compound 57) (100 mg/kg; p.o.; daily; 34 consecutive days) achieves 42% tumor growth inhibition in MDA-MB-436 xenografts[1].
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.

Animal Model: NOD-SCID mice[1]
Dosage: 100 mg/kg
Administration: p.o.; daily; 34 consecutive days
Result: Achieved a tumor growth inhibition (TGI) of 42%.
Markedly increased ubiquitinated PCNA (ub-PCNA) and γ-H2AX levels in xenograft tumor tissues.
Animal Model: Balb/c mice (female, 6−8 weeks old, 18−22 g)[1]
Dosage: 100 mg/kg; 300 mg/kg
Administration: p.o.; daily; 30 days
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.
Animal Model: Balb/c mice (female, 6−8 weeks old, 18−22 g)[1]
Dosage: 400 mg/kg; 600 mg/kg; 800 mg/kg
Administration: p.o.; single dose
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.
Animal Model: Sprague-Dawley rats[1]
Dosage: 10 mg/kg
Administration: p.o.; single dose
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%.
Molecular Weight

521.49

Formula

C26H22F3N7O2
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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USP1-IN-18 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

USP1-IN-183064481-29-1DeubiquitinaseDNA/RNA SynthesisDUBsratsPCNAHCC1937DNA damageSUM149PTUSP1-UAF1 complexG2-M phase cell cycle arresttriple-negative breast cancerMDA-MB-436replication stressInhibitorinhibitorinhibit

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