parylation

Talazoparib (LT-673) is a new-type PARP inhibitor (IC50: 0.58 nM), It similarly binds to PARP1/2 (Kis: 1.2/0.85 nM).

COH34 (1-[(E)-(4-methylphenyl)sulfanyliminomethyl]naphthalen-2-ol) is a selective inhibitor of PARG with an IC50 of 0.37 nM and a Kd of 0.547 μM. COH34 prolongs PARylation at DNA lesions and traps DNA repair factors.

(rac)-Talazoparib ((rac)-BMN-673) (Compound 47) is an orally active inhibitor of PARP1/2, with Ki values of 1.2 nM and 0.87 nM, respectively. It inhibits cellular PARylation at an EC50 of 2.51 nM. This compound leads to the accumulation of DNA damage and suppresses the proliferation of BRCA1/2-mutated MX-1 and Capan-1 cells, with IC50 values of 0.3 nM and 5 nM, respectively. Additionally, (rac)-Talazoparib exhibits antitumor activity in mouse models.

PARP1-IN-44 is a derivative of Olaparib and functions as an orally active PARP1 inhibitor with an IC50 of 0.6 nM. It also inhibits PARP2 (IC50 = 1.0 nM) and PARP7 (IC50 = 7.5 nM). PARP1-IN-44 demonstrates selective antiproliferative activity against BRCA-deficient cancer cells with minimal toxicity to normal cells. It induces G2/M phase arrest, promotes apoptosis, increases reactive oxygen species (ROS) levels, and disrupts mitochondrial membrane potential. Additionally, PARP1-IN-44 inhibits PARylation and leads to the accumulation of γH2AX. It activates the cGAS-STING pathway, enhancing the expression of IFN-β and CXCL10. In a CT26 tumor mouse model, PARP1-IN-44 enhances CD8+ T cell infiltration, showcasing significant in vivo antitumor activity.

Etidaligide is a DNA repair inhibitor designed to prevent the repair of DNA damage in tumor cells. It also activates DNA-dependent protein kinases (DNA-PK) and poly (ADP-ribose) polymerases, enzymes that promote the phosphorylation of H2AX and the parylation of proteins.

2-Azido-NAD, an analog of NAD+, is utilized for visualizing the intracellular poly (ADP-ribosyl)ation (PARylation) process.