Poly [ADP-ribose] polymerase 7 (PARP7) (PARP7)

Poly [ADP-ribose] polymerase 7 (PARP7), also known as TIPARP, is a mono-ADP-ribosyltransferase that serves as a key negative regulator of the innate immune response and cellular stress pathways [1, 11]. It functions by catalyzing the mono-ADP-ribosylation of specific substrates, including TBK1 and IRF3, which effectively suppresses the Type I interferon (IFN-I) signaling pathway and facilitates tumor immune evasion [7, 10]. PARP7 is frequently upregulated or amplified in various malignancies, such as squamous cell lung cancer and breast cancer, where it correlates with poor prognosis [16, 22]. Therapeutic targeting of PARP7 with selective small-molecule inhibitors, such as RBN-2397, restores the IFN-I response, promotes the infiltration of cytotoxic T cells, and induces immunogenic cell death [6, 12]. Beyond its immunological role, PARP7 is involved in a negative feedback loop with the aryl hydrocarbon receptor (AhR) and modulates the activity of nuclear receptors like the estrogen and androgen receptors [3, 8]. Current clinical development focuses on PARP7 inhibitors as potent agents for treating advanced solid tumors, both as monotherapies and in combination with immune checkpoint blockades [13, 18].

Other names

TIPARPARTD142,3,7,8-tetrachlorodibenzo-p-dioxin-inducible poly-ADP-ribose polymeraseADP-ribosyltransferase diphtheria toxin-like 14

PARP7 inhibition; Restoration of Type I interferon signaling; Activation of innate and adaptive anti-tumor immunity; Stabilization of alpha-tubulin.