GeA-69

GeA-69 (CAS No.: 2143475-98-1) is a selective allosteric inhibitor of poly(ADP-ribose) polymerase 14 (PARP14), a member of the PARP family implicated in mono-ADP-ribosylation and regulation of DNA damage responses, immune signaling, and transcriptional control. This small molecule specifically targets the macrodomain 2 (MD2) of PARP14, interfering with its ability to recognize ADP-ribosylated substrates and thereby modulating downstream signaling events associated with DNA repair processes. Biochemical and cellular studies demonstrate that GeA-69 binds to PARP14 MD2 with affinity in the low micromolar to submicromolar range and effectively inhibits the recruitment and relocalization of PARP14 to sites of DNA damage, including laser-induced lesions in cultured cells. Functionally, GeA-69 reduces macrodomain-dependent activity in cellular systems, with partial inhibition observed at moderate micromolar concentrations and more complete suppression at higher exposure levels. As a targeted probe for PARP14 macrodomain biology, GeA-69 is widely used in mechanistic studies of ADP-ribose signaling, DNA damage repair pathways, and epigenetic regulation, as well as in early-stage drug discovery efforts aimed at modulating PARP-mediated processes; experimental concentrations vary depending on cell type, assay format, and specific research objectives.