ART558

ART558 is a nanomolar potent, selective, low molecular weight, allosteric DNA polymerase activity of Polθ inhibitor ( IC 50 =7.9 nM). ART558 can be used for the research of cancer 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: BRCA2 wild-type or BRCA2 ‒/‒ cells Concentration: 0~10 μM Incubation Time: 7 days Result: Showed synthetic lethality and a combinatorial effect with the PARPi olaparib in previously described isogenic models of BRCA1-deficiency. Western Blot AnalysisCell Line: BRCA2 wild-type or BRCA2 ‒/‒ cells Concentration: 5μM Incubation Time: 0~72 hours Result: Showed γH2AX accumulation in cells. Form:Solid IC50& Target:IC50: 7.9 nM (Polθ)

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