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。
货号:ajcx33950
CAS:2603528-97-6
分子式:C21H21F3N4O2
分子量：418.41
溶解度:N/A
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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[1].

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

[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.