PDD00017273 is a radiosensitizing PARG) inhibitor with antitumor or activity for the study of epithelial ovaries.

PARG:1.45 nM (Kd), PARG:26 nM

PDD 00017273 is an effective inhibitor of PARG with an IC50 of 26 nM and a KD of 1.45 nM. At 10 μM, PDD 00017273 does not inhibit five common cytochrome P450 enzymes. At 30 μM, it moderately increases phosphorylated H2AX (γH2AX) intensity. Additionally, PDD 00017273 reduces NAD/H through PARG inhibition after DNA damage. The compound inhibits ZR-75-1 cells carrying wild-type BRCA1 and BRCA2 and exhibits weaker activity against MDA-MB-436 cells carrying the 5396 + 1G>A mutation in BRCA1[2].At 0.3 μM, PDD 00017273 inhibits the degradation of PAR polymers in MCF7 cells. It also reduces the viability of BRCA1, BRCA2, PALB2, FAM175A, and BARD1-depleted cells. PDD 00017273 halts replication forks and induces DNA damage requiring homologous recombination (HR) for repair[1].