ART558 是一种高效的、选择性的、变构 DNA 聚合酶活性的 Polθ 抑制剂，IC50为7.9 nM。ART558 可用于癌症研究。

ART558 is a 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.

ART558 (5μM; 0~72 hours; BRCA2wild-type or BRCA2-/- cells) shows γH2AX accumulation in cells. 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 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[1].

2603528-97-6

C21H21F3N4O2

418.41

DMSO:150 mg/mL (358.5 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years