PDD00017273

PDD00017273 is a potent, selective, and cell-permeable small molecule **inhibitor of poly(ADP-ribose) glycohydrolase (PARG)**, with an IC50 of 26 nM and KD of 1.45 nM[1][3][5][7][13][14][15]. PDD00017273 demonstrates >350-fold selectivity for PARG over related enzymes like PARP1 and ARH3, and does not significantly inhibit several cytochrome P450 enzymes at 10 μM[7][13]. It acts by blocking PARG-mediated dePARylation processes, resulting in the **accumulation of PARylated proteins**, stalling DNA replication forks, increasing DNA damage, and ultimately reducing cell viability especially in DNA damage-response deficient tumor cells[1][13][6][11]. The compound is used primarily as a tool compound in preclinical research and has not advanced to clinical development due to poor bioavailability[11][13]. Its effects have been explored especially in the context of **cancer research**, including the synthetic lethality with homologous recombination repair-deficient (HRD) cancers and synergistic cytotoxicity when combined with other DNA damage response inhibitors[4][11].