Mono-ADP-ribosyltransferase PARP7 (PARP7)

Mono-ADP-ribosyltransferase PARP7, also known as TIPARP, is an enzyme within the poly(ADP-ribose) polymerase (PARP) family that catalyzes mono-ADP-ribosylation (MARylation), the transfer of a single ADP-ribose unit to target proteins [1, 4]. It functions as a critical negative regulator of the innate immune system by suppressing Type I interferon (IFN) signaling, notably through the modification of TANK-binding kinase 1 (TBK1) [1, 9]. In many cancers, including lung, breast, and prostate malignancies, PARP7 is overexpressed or amplified, enabling tumor cells to evade immune detection by silencing the "don't kill me" signals typically triggered by cellular stress [2, 8]. Small-molecule inhibitors such as RBN-2397 (atamparib) target the catalytic activity of PARP7 to restore IFN signaling and promote a robust anti-tumor immune response [4, 6]. These therapeutic agents are currently under clinical investigation as both monotherapies and in combination with immune checkpoint inhibitors for advanced solid tumors [13, 16]. Additionally, PARP7 plays significant roles in regulating aryl hydrocarbon receptor (AHR) signaling and modulating host responses to viral infections [1, 10].

Other names

TIPARPTCDD-inducible poly-ADP-ribose polymeraseARTD14Diphtheria toxin-like ADP-ribosyltransferase 142,3,7,8-tetrachlorodibenzo-p-dioxin-inducible poly(ADP-ribose) polymerase

Inhibition of PARP7 catalytic activity (NAD+ competitive), restoration of Type I interferon signaling, and induction of PARP7 trapping on chromatin.