Art. -Nr.: HY-189455

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.

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CAS. Nr.: 3094127-54-2
Formel: C₂₈H₂₅F₃N₆O
Molecular Weight:518.53

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

USP1-IN-20 Chemical Structure

CAS. Nr.: 3094127-54-2

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Protokoll (6)
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

^[1]

USP1

3.0 nM (IC₅₀)

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Cellular Effect

Cell Line	Type	Value	Description	References
MDA-MB-436	GI₅₀	16.2 nM	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.	acs.jmedchem.6c01009
MDA-MB-436	IC₅₀	11.5 nM	Inhibition of colony formation in BRCA1-deficient MDA-MB-436 cells. Inhibition of colony formation in BRCA1-deficient MDA-MB-436 cells.	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. Further protocols information, click here.

Cell Cycle Analysis^[1]

View Protocol

Cell Line:

MDA-MB-436 cells
Concentration:

30, 300, 1000 nM
Incubation Time:

24 h
Result:

Dose-dependently induced significant G2/M phase cell cycle arrest (arrest rate increased from 19.4% to 34.3%).

Western Blot Analysis^[1]

View Protocol

Cell Line:

MDA-MB-436 cells
Concentration:

30, 100, 300, 1000 nM
Incubation Time:

24 h
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

Species	Dose	Route	T_1/2	T_max	C_max	AUC_0-t	F	MRT_0-t	CL
Mice^[1]	10 mg/kg	p.o.	2.7 h	0.33 h	1803.5 ng/mL	2361.9 ng·h/mL	49.3 %	/	/
Mice^[1]	10 mg/kg	i.v.	0.6 h	0.08 h	8356.4 ng/mL	4791.6 ng·h/mL	/	/	/
Mice^[2]	100 mg/kg	p.o.	2.18 h	1.75 h	7249.1 ng/mL	57244.8 ng/mL·h	/	5.26 h	1.90 L/h/kg

In Vivo

USP1-IN-20 (compound 38 a) (50-100 mg/kg; oral administration; once daily; 34 days) dose-dependently inhibited tumor growth in a BRCA1-deficient MDA-MB-436 subcutaneous xenograft NOD-SCID mouse model, exhibited extremely strong synergistic antitumor activity in combination with Olaparib (HY-10162), and significantly upregulated Ub-PCNA, P27, P21, and γ-H2AX levels within tumor tissues^[1].
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.

Animal Model:

NOD-SCID mice^[1]
Dosage:

50 mg/kg, 100 mg/kg
Administration:

p.o.; once daily; 34 days
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.

Animal Model:

NOD-SCID mice^[1]
Dosage:

100 mg/kg
Administration:

p.o.; once daily; 27 days
Result:

Suppressed tumor growth with a TGI rate of 64.7%.
Maintained stable or increased body weight over the treatment period.

Animal Model:

Mice^[1]
Dosage:

100 mg/kg, 300 mg/kg
Administration:

p.o.; once daily; 4 weeks
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

CAS. Nr. 3094127-54-2
Molecular Weight 518.53
Formel C₂₈H₂₅F₃N₆O
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Protokoll

All Cell Biology Animals and Diseases

Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
PCNA Immunodetection Proliferation Assay
PCNA immunodetection measures proliferative activity by detecting proliferating cell nuclear antigen, a nuclear protein associated with DNA polymerase δ function and DNA replication. The assay readout is the proportion of PCNA-positive nuclei among total counted cells, but PCNA labeling is not identical to BrdU labeling because PCNA can mark late G1/early S-associated replication competence and may persist beyond active DNA synthesis depending on fixation and extraction conditions.
Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[1]. Yang T, et al. Optimization of a Series of Novel 1H-Pyrrolo[3,2-c]pyridine-Based USP1 Inhibitors with Potent In Vivo Antitumor Activity. J Med Chem. 2026;69(17):20403-20432.

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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USP1-IN-20

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