ART558 free base · Synonyms: ART-558 · ART 558

ART558 is a nanomolar potent, selective, low molecular weight, allosteric DNA polymerase activity of Polθ inhibitor.

For research use only. Not for human or veterinary use.

Target DNA/RNA Synthesis

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

ART558 structure

CAS No.: 2603528-97-6

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
50 mg	USD 450.00	BP-02034-50mg	In stock	Get quote
100 mg	USD 675.00	BP-02034-100mg	In stock	Get quote
250 mg	USD 1,150.00	BP-02034-250mg	In stock	Get quote
500 mg	Inquire	BP-02034-500mg	In stock	Inquire
1 g	Inquire	BP-02034-1g	In stock	Inquire

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Description

ART558 is a nanomolar potent, selective, low molecular weight, allosteric DNA polymerase activity of Polθ inhibitor (IC50=7.9 nM). ART558 can be used for the research of cancer.

Biological activity

In Vitro ART558 (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. ART558 (5 μM; 0-72 hours; BRCA2wild-type or BRCA2-/- cells) shows γH2AX accumulation in cells. ART558 inhibits the major Polθ mediated DNA repair process, Theta-Mediated End Joining, without targeting NonHomologous End Joining. ART558 elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor. ART558 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 increases the residence time of YFP-tagged full-length Polθ at sites of laserinduced DNA damage.

Identifiers

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
InChIKey: YHMDHAMZFMNMTF-MSOLQXFVSA-N

Specifications

MW (average): 418.4122
Formula: C₂₁H₂₁F₃N₄O₂
CAS No.: 2603528-97-6
Physical state: Solid
Color: White to off-white
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder 4°C, sealed storage, away from moisture and light; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO 170 mg/mL

Documents

References

[1]. Zatreanu D, et al. Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance. Nat Commun. 2021 Jun 17;12(1):3636.

Same target

Search DNA/RNA Synthesis

Same research area

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