RBN012759 (RBN-012759) is a potent and highly selective PARP14 chemical probe inhibitor with biochemical IC50 of 3 nM in TR-FRET assays, >300-fold selectivity over all PARP family members.
RBN-012759 is an in vivo chemical probe that selectively engages PARP14 in tissue.
RBN-012759 shows binding affinity for PARP14 with Kd value of 2 nM determined by surface plasmon resonance (SPR), inhibits mouse PARP14 TR-FRET probe displacement assay with an IC50 value of 5 nM, which is comparable with its human PARP14 potency (IC50=3 nM).
RBN-012759 rubustly inhibits PARP14-specific self-MARylation in IFN-γ-stimulated primary human macrophages.
RBN-012759 reversed IL-4-driven gene expression in M2-like macrophages, including CD209, MMP-1 and CLTC. RBN-012759 also decreased the protein level of three M2-like proteins, IL-10, CCL24, and IL1-ra, in the supernatants of IL-4-stimulated macrophages.
RBN012759 induced antitumor inflammation in kidney cancer tumor explant models, elicited similar gene expression changes.