ART558

Research use only, not for human use.

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 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.(In Vitro):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.

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 (5μM; 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. Cell Viability Assay Cell Line:BRCA2wild-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 Analysis Cell Line:BRCA2wild-type or BRCA2?/? cells Concentration:5μM Incubation Time:0~72 hours Result:Showed γH2AX accumulation in cells.

——

——

Cell Cycle/DNA Damage

DNA/RNA Synthesis

ACSS2

——

——

2603528-97-6

418.41

C21H21F3N4O2

>98% (HPLC)

In Vitro:?DMSO : 170 mg/mL (406.30 mM)

C(N(C)C1=CC(C)=CC=C1)(=O)[C@H]2N(CC[C@H]2O)C3=C(C#N)C(C(F)(F)F)=CC(C)=N3

——

(-20℃)

With Ice Pack

≥ 2 years