For research use only. Not for therapeutic Use.
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].
| Catalog Number | I045272 |
| CAS Number | 2603528-97-6 |
| Synonyms | (2S,3R)-1-[3-cyano-6-methyl-4-(trifluoromethyl)pyridin-2-yl]-3-hydroxy-N-methyl-N-(3-methylphenyl)pyrrolidine-2-carboxamide |
| Molecular Formula | C21H21F3N4O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C21H21F3N4O2/c1-12-5-4-6-14(9-12)27(3)20(30)18-17(29)7-8-28(18)19-15(11-25)16(21(22,23)24)10-13(2)26-19/h4-6,9-10,17-18,29H,7-8H2,1-3H3/t17-,18+/m1/s1 |
| InChIKey | YHMDHAMZFMNMTF-MSOLQXFVSA-N |
| SMILES | CC1=CC(=CC=C1)N(C)C(=O)C2C(CCN2C3=NC(=CC(=C3C#N)C(F)(F)F)C)O |
| Reference | [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. |
