ART558 (GMP) is ART558 (HY-141520) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. ART558 is a potent, selective and allosteric DNA polymerase theta (Polθ) inhibitor (IC50=7.9 nM). ART558 elicits BRCA-gene synthetic lethality and DNA damage. ART558 can be used for the research of cancer, such as breast cancer.
For research use only. We do not sell to patients.
- CAS No.: 2603528-97-6
- Formula: C21H21F3N4O2
- Molecular Weight:418.41
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All DNA/RNA Synthesis Isoforms
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Biological Activity
Description
IC50 & Target
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DNA Polymerase |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| DLD-1 | EC50 |
>12 μM
Compound: 22; ART558
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Antiproliferative activity against human DLD-1 cells
Antiproliferative activity against human DLD-1 cells
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[PMID: 36200480] |
| DLD-1 | EC50 |
0.8 nM
Compound: 22; ART558
|
Antiproliferative activity against human BRCA-2 deficient DLD-1 cells
Antiproliferative activity against human BRCA-2 deficient DLD-1 cells
|
[PMID: 36200480] |
| HEK293 | EC50 |
180 nM
Compound: 22; ART558
|
Inhibition of microhomology-mediated end joining in HEK293 cells
Inhibition of microhomology-mediated end joining in HEK293 cells
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[PMID: 36200480] |
In Vitro
ART558 (GMP) (0-10 μM; 7 days; BRCA2wild-type or BRCA2-/- cells) shows synthetic lethality and a combinatorial effect with the PARPi olaparib in previously described isogenic models of BRCA1-deficiency[1].
ART558 (GMP) (5 μM; 0-72 hours; BRCA2wild-type or BRCA2-/- cells) shows γH2AX accumulation in cells[1].
ART558 (GMP) inhibits the major Polθ mediated DNA repair process, Theta-Mediated End Joining, without targeting NonHomologous End Joining. ART558 (GMP) elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor[1].
ART558 (GMP) increases biomarkers of single-stranded DNA and synthetic lethality in 53BP1-defective cells whilst the inhibition of DNA nucleases that promote end-resection reversed these effects, implicating these in the synthetic lethal mechanism-of-action. ART558 (GMP) increases the residence time of YFP-tagged full-length Polθ at sites of laserinduced DNA damage[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Chemical Information
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CAS No. 2603528-97-6
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Molecular Weight 418.41
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Formula C21H21F3N4O2
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SMILES
CN(C1=CC(C)=CC=C1)C([C@H]2N(C3=C(C(C(F)(F)F)=CC(C)=N3)C#N)CC[C@H]2O)=O
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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.
Protocols
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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.
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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.
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)