| Description | PDD00017273 is a radiosensitizing PARG) inhibitor with antitumor or activity for the study of epithelial ovaries. |
| In vitro | 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]. |
| Target activity | PARG:1.45 nM (Kd), PARG:26 nM |
| molecular weight | 514.62 |
| Molecular formula | C23H26N6O4S2 |
| CAS | 1945950-21-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 20 mg/mL (38.86 mM), Sonication is recommended. |
| References | 1. Gravells P, et al. Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase. DNA Repair (Amst). 2017 Apr;52:81-91. 2. James DI, et al. First-in-Class Chemical Probes against Poly(ADP-ribose) Glycohydrolase (PARG) Inhibit DNA Repair with Differential Pharmacology to AZD2281. ACS Chem Biol. 2016 Nov 18;11(11):3179-3190. Epub 2016 Oct 12. |
| Citations | 1. Sun Y, Chen J, Pommier Y.Real-time imaging of drug-induced trapping of cellular topoisomerases and poly (ADP-ribose) polymerase 1 at the single-molecule level.Nucleic Acids Research.2023: gkad735. |