ART558 

ART558 (GMP) is ART558 (HY-141520) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. ART558 is a potent, selective and allosteric DNA polymerase theta (Polθ) inhibitor (IC₅₀=7.9 nM). ART558 elicits BRCA-gene synthetic lethality and DNA damage. ART558 can be used for the research of cancer, such as breast cancer^[1].

ART558 (GMP) (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^[1].
ART558 (GMP) (5 μM; 0-72 hours; BRCA2^wild-type or BRCA2^-/- cells) shows γH2AX accumulation in cells^[1].
ART558 (GMP) inhibits the major Polθ mediated DNA repair process, Theta-Mediated End Joining, without targeting NonHomologous End Joining. ART558 (GMP) elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor^[1].
ART558 (GMP) 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 (GMP) increases the residence time of YFP-tagged full-length Polθ at sites of laserinduced DNA damage^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

418.41

C₂₁H₂₁F₃N₄O₂

2603528-97-6

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

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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.  [Content Brief]