ART558

ART558 is an inhibitor of DNA polymerase theta (Poltheta, IC50 = 7. nM for Poltheta polymerase activity). It is selective for the polymerase activity of Poltheta over its ATPase activity (IC50 = >12 µM). ART558 (0. 0. and 1 µM) inhibits the repair of DNA double-strand breaks via theta-mediated end joining (TMEJ), but not non-homologous end joining (NHEJ), in a reporter assay using an extrachromosomal DNA substrate. It induces synthetic lethality in RPE1 cells lacking BRCA1 and DLD-1 cells lacking BRCA2. ART558 also reduces tumor growth in a 3D organoid culture model using cells derived from patients with BRCA1-low, 53BP1-low prostate cancer.. Solulibility: DMSO: Soluble: =10 mg/ml: Ethanol: Sparingly Soluble: 1-10 mg/ml.