PARP-7 Inibitori

I comuni inibitori di PARP-7 includono, ma non solo, Rucaparib CAS 283173-50-2, Olaparib CAS 763113-22-0, Veliparib CAS 912444-00-9, Talazoparib CAS 1207456-01-6 e Ceralasertib CAS 1352226-88-0.

Chemical inhibitors of PARP-7 act by different mechanisms to prevent the function of the protein, which is critical in the DNA damage repair pathway. Rucaparib, Olaparib, Veliparib, Talazoparib, Niraparib, Pamiparib, and AZD2461 act by binding to the NAD+ binding site of PARP-7. This binding mimics the structure of NAD+ and competitively inhibits the catalytic activity of the enzyme, thus preventing PARP-7 from playing its role in ADP-ribosylation of target proteins. This interference with the ADP-ribosylation process is crucial because it blocks the repair of single-strand DNA breaks, an essential function of PARP-7. Talazoparib, in particular, traps PARP-7 on DNA where damage occurs, amplifying inhibition not only by blocking enzyme activity, but also by blocking the enzyme in a complex with DNA, which exacerbates inhibition of DNA repair.

In addition, UPF-1069, PJ34, INO-1001, 3-aminobenzamide, and AG14361 share a common inhibitory tactic: these chemicals bind directly to the active site of PARP-7, effectively hindering its enzymatic function. UPF-1069 and PJ34 occupy the NAD+ binding site, directly preventing PARP-7 from performing its normal ADP-ribosyltransferase activity. INO-1001 and 3-aminobenzamide mimic the structure of nicotinamide, a part of the NAD+ molecule, resulting in competitive inhibition. AG14361 excels at binding to the catalytic site of PARP-7, blocking the critical transfer of ADP-ribose units to acceptor proteins required for DNA repair. By inhibiting this transfer, AG14361 disrupts the PARP-dependent DNA damage response, reflecting the substance's potent inhibitory effect on the function of PARP-7 in cellular processes.