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ART558

CAS No. : 2603528-97-6

MCE 站：ART558

产品活性：ART558 是一种纳摩尔、高效、有选择性、低分子量、变构 DNA 聚合酶活性的 Polθ 抑制剂(IC₅₀=7.9 nM)。ART558 可用于癌症研究。

研究领域：Others

作用靶点：Others

In Vitro: ART558 (0~10 μM; 7 days; BRCA2^wild-type or BRCA2^‒/‒ cells) shows synthetic lethality ａnd a combinatorial effect with the PARPi olaparib in previously described isogenic models of BRCA1-deficiency.
ART558 (5μM; 0~72 hours; BRCA2^wild-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.

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