PARP-16 Inhibitors

Chemical inhibitors of PARP-16 are a diverse group of compounds that interfere with the protein's enzymatic activity, specifically its role in facilitating ADP-ribosylation, which is crucial in DNA damage response and repair mechanisms. PJ-34, for example, is a potent inhibitor that binds to the catalytic domain of PARP-16, preventing the poly(ADP-ribosylation) activity that is a signature function of the enzyme. Similarly, Olaparib targets PARP-16 by occupying the NAD+ binding site, obstructing the synthesis of poly(ADP-ribose) and thus inhibiting the protein's function. Veliparib and Rucaparib operate by binding to the active site of PARP-16, impeding the protein's ability to carry out its role in the repair of damaged DNA.

Continuing with the theme of active site inhibition, Talazoparib inhibits PARP-16 by trapping the PARP-DNA complex, thereby hindering the protein's activity. Niraparib selectively binds to PARP-16, blocking its essential ADP-ribosyltransferase activity. INO-1001 and 3-Aminobenzamide both exhibit their inhibitory action by competing with NAD+ for binding sites on PARP-16, thus inhibiting the ADP-ribosylation process that is essential for the protein's function. NU1025 also inhibits PARP-16 by interfering with its ability to synthesize poly(ADP-ribose), a molecule crucial for PARP-16's signaling role. AG14361 prevents the ADP-ribosylation activity of PARP-16, a necessary function for its involvement in DNA damage repair pathways. Furthermore, GPI 15427 and AZD2461 inhibit PARP-16 by binding to its catalytic domain and the NAD+ site, respectively, which are critical for the transfer of ADP-ribose to target proteins, a fundamental action required for PARP-16's enzymatic activity. Each of these chemicals disrupts the function of PARP-16 through distinct yet effective mechanisms, ultimately inhibiting the protein's ability to participate in its normal biological processes.