ART5537
Based on 1 Customer Validation
ART5537 is a selective EXO1 inhibitor with a IC50 of 3.4 nM and a Kd of 6.8 nM. ART5537 exerts cellular homologous recombination (HR) inhibition with EC50 of 7.2 nM in HAP1 parental cells. ART5537 shows >200-fold selectivity over a panel of the wider nuclease superfamily. ART5537 exerts biological effects that are exclusively driven by EXO1 inhibition. ART5537 demonstrates sensitization to ionizing radiation and synergy with Olaparib (HY-10162). ART5537 can be used for research in breast cancer and colorectal adenocarcinoma.
For research use only. We do not sell to patients.
- Purity : 99.84%
- Formula: C23H18ClN5O3
- Molecular Weight:447.87
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
ART5537 (0.0001-10 μM) displays unambiguous dose-dependent cellular target engagement with an EC50 = 55 nM[1].
ART5537 (0.001-10 μM) has no activation HAP1 EXO1 KO cells, shows no further effect over KO of EXO1 (∼ 50% reduction) and induces a dose-dependent retention of GPF2-EXO1 on chromatin in a U-2 OS Flp-In line [1].
ART5537 (7 days) is not a broadly cytotoxic and has a mild EXO1-dependent sensitivity in MDA-MB-436 (EC50 = 4.0 nM), HCC 1937 (EC50 = 5.3 nM), SUM 149PT (EC50 = 5.0 nM) and HCC38 (EC50 = 8.3 nM) cells[1].
ART5537 (5 days) exhibits no ubiquitous cytotoxicity in HCT116 cells following cotreatment with Olaparib (HY-10162) [1].
ART5537 (7 days) combined with Olaparib exerts a strong synergistic effect in radiation-treated wild-type HCT116 cells, but no such effect is observed in the two radiation-treated EXO1 knockout clones[1].
ART5537 (0.01-100 μM, 6 days) effectively inhibits EXO1, and when combined with Olaparib in radiation-treated HCT116 cells, it significantly enhances the cancer cell-killing effect and greatly increases the activity potency[1].
ART5537 inhibits EXO1 in HCT116 cells and results in a > 40-fold sensitization, has suitable physicochemical properties for use as a cell probe with high thermodynamic solubility and good passive permeability and is unstable in human and mouse liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HCT116 cells
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Concentration:0.01, 0.1, 10 and 100 μM
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Incubation Time:6 days
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Result:Resulted a > 40-fold sensitization.
Potently sensitized cells irradiated with 3 × 1 Gy (EC50 = 144 nM).
Parmacokinetics
| Species | Dose | Route | CL_obs | T1/2 | Vss |
|---|---|---|---|---|---|
| Mice[1] | 0.2 mg/kg | i.v. | 111 mL/min/kg | 0.7 h | 5.7 L/kg |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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Appearance Solid
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Molecular Weight 447.87
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Formula C23H18ClN5O3
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Color White to off-white
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SMILES
C[C@@H](C1=CC=CC=C1)N2CN(C3=NC=C(Cl)C4=C3C=NC=C4)N5C=CC(C(O)=C5C2=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (111.64 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Protocols
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CRISPR-Cas9 HDR knock-in/precise editing
CRISPR-Cas9 HDR knock-in uses a guide RNA to direct Cas9 to a genomic target adjacent to a PAM, where Cas9 creates a double-strand break; if a donor DNA template with homology to the cut region is present, cellular HDR can copy the donor sequence into the genome, producing a precise substitution, tag, reporter, or insertion rather than an indel. The readout is the fraction of alleles or cells carrying the intended donor-derived edit, measured by junction PCR, restriction-fragment analysis, Sanger sequencing, amplicon deep sequencing, flow cytometry for reporter knock-in, or clone genotyping; NHEJ indels and partial or non-HDR insertions are measured in parallel because they compete with or confound precise HDR outcomes.
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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.
Purity & Documentation
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Data Sheet (280 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2328 mL | 11.1640 mL | 22.3279 mL | 55.8198 mL |
| 5 mM | 0.4466 mL | 2.2328 mL | 4.4656 mL | 11.1640 mL | |
| 10 mM | 0.2233 mL | 1.1164 mL | 2.2328 mL | 5.5820 mL | |
| 15 mM | 0.1489 mL | 0.7443 mL | 1.4885 mL | 3.7213 mL | |
| 20 mM | 0.1116 mL | 0.5582 mL | 1.1164 mL | 2.7910 mL | |
| 25 mM | 0.0893 mL | 0.4466 mL | 0.8931 mL | 2.2328 mL | |
| 30 mM | 0.0744 mL | 0.3721 mL | 0.7443 mL | 1.8607 mL | |
| 40 mM | 0.0558 mL | 0.2791 mL | 0.5582 mL | 1.3955 mL | |
| 50 mM | 0.0447 mL | 0.2233 mL | 0.4466 mL | 1.1164 mL | |
| 60 mM | 0.0372 mL | 0.1861 mL | 0.3721 mL | 0.9303 mL | |
| 80 mM | 0.0279 mL | 0.1395 mL | 0.2791 mL | 0.6977 mL | |
| 100 mM | 0.0223 mL | 0.1116 mL | 0.2233 mL | 0.5582 mL |
ART5537 Related Classifications
HY-180573 Related Classifications
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