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Chemical Structure| 2603528-97-6 Chemical Structure| 2603528-97-6

Structure of ART558
CAS No.: 2603528-97-6

Chemical Structure| 2603528-97-6

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ART558 is a Polθ inhibitor that specifically interferes with Polθ function. It shows great application potential in cancer research and DNA repair mechanism studies.

4.5 *For Research Use Only !

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Product Details of ART558

CAS No. :2603528-97-6
Formula : C21H21F3N4O2
M.W : 418.41
SMILES Code : O=C([C@H]1N(C2=NC(C)=CC(C(F)(F)F)=C2C#N)CC[C@H]1O)N(C)C3=CC=CC(C)=C3
MDL No. :N/A

Safety of ART558

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Related Pathways of ART558

DNA

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Glioblastoma cells (GBM21) 56.5 µM 120 hours ART558 significantly decreases glioblastoma cell viability, induces apoptosis, and is accompanied by a reduction in cell proliferation and DNA damage. Int J Mol Sci. 2024 Aug 23;25(17):9134.
Normal Human Astrocytes (NHA) 56.5 µM 120 hours ART558 has a much lower impact on normal human astrocytes, especially in terms of cell viability and DNA damage. Int J Mol Sci. 2024 Aug 23;25(17):9134.
DLD1 BRCA2‒/‒cells 5 µM 24-120 hours ART558 induced DNA damage in BRCA2-deficient cells, evidenced by increased γH2AX foci. Nat Commun. 2021 Jun 17;12(1):3636.
RPE1 BRCA1‒/‒cells 0.5 µM 7 days ART558 elicited synthetic lethality in BRCA1-deficient cells and showed combinatorial effects with the PARP inhibitor olaparib. Nat Commun. 2021 Jun 17;12(1):3636.
Brca1C61G/C61G53bp1−/−cells 10 µM Investigated the effect of ART558 on Brca1C61G/C61G53bp1−/−cells, showing that ART558 suppressed G2/M DNA synthesis, and RAD52 inhibition could not restore DNA synthesis. Nat Commun. 2023 Nov 29;14(1):7834.
53bp1−/−cells 10 µM Investigated the effect of ART558 on 53bp1−/−cells, showing that ART558 suppressed G2/M DNA synthesis, but RAD52 inhibition could restore DNA synthesis. Nat Commun. 2023 Nov 29;14(1):7834.
Human airway basal stem cells (ABCs) 5 µM To evaluate if combining ART558 with AZD7648 further improves gene insertion efficiency, results showed improved gene insertion but induced toxicity. Mol Ther Nucleic Acids. 2024 Sep 16;35(4):102339.
HCT116 1  µM and 3 µM ART558 does not cause any effect in the absence of IR but effectively radiosensitizes all three BRCA-proficient cell lines from 1 mmol/L concentration. Clin Cancer Res. 2023 Apr 14;29(8):1631-1642.
H460 1  µM and 3 µM ART558 does not cause any effect in the absence of IR but effectively radiosensitizes all three BRCA-proficient cell lines from 1 mmol/L concentration. Clin Cancer Res. 2023 Apr 14;29(8):1631-1642.
T24 1  µM and 3 µM ART558 does not cause any effect in the absence of IR but effectively radiosensitizes all three BRCA-proficient cell lines from 1 mmol/L concentration. Clin Cancer Res. 2023 Apr 14;29(8):1631-1642.
U2OS WT 3 µM U2OS WT cells were significantly radiosensitized, whereas U2OS Pol q KO cells were not radiosensitized, confirming that the radiosensitizing effect of ART558 is Pol q-specific. Clin Cancer Res. 2023 Apr 14;29(8):1631-1642.
U2OS Pol q KO 3 µM U2OS Pol q KO cells were not radiosensitized by ART558, further confirming that the radiosensitizing effect of ART558 is Pol q-specific. Clin Cancer Res. 2023 Apr 14;29(8):1631-1642.
RPE1 TP53‒/‒BRCA1‒/‒cells 0.5 μM 7 days Evaluate ART558 sensitivity in BRCA1-deficient cells, results showed significant reduction in cell survival Nat Commun. 2021 Jun 17;12(1):3636.
DLD1 BRCA2‒/‒cells 5 μM 5 days Evaluate ART558 sensitivity in BRCA2-deficient cells, results showed significant reduction in cell survival Nat Commun. 2021 Jun 17;12(1):3636.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rats MDA-MB-436 BRCA1 mutant SHLD2‒/‒xenografts 100 mg/kg Daily administration for 76 days ART812 significantly inhibited tumor growth and was well-tolerated. Nat Commun. 2021 Jun 17;12(1):3636.
Nu/Nu mice HCT116 subcutaneous xenograft model Oral 150 mg/kg Twice daily for 12 days The combination of ART899 with fractionated radiation (10×2 Gy) significantly improved tumor growth delay and was well tolerated. Clin Cancer Res. 2023 Apr 14;29(8):1631-1642.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.39mL

0.48mL

0.24mL

11.95mL

2.39mL

1.20mL

23.90mL

4.78mL

2.39mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
 

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