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RBN-012759 is an inhibitor of poly(ADP-ribose) polymerase 14 (PARP14; IC50 = 0.003 µM).1 It is selective for PARP14 over PARP1-4, -5a, -5b, -6-12, -15, and -16 (IC50s = 1->100 µM). RBN-012759 (10 µM) inhibits IFN-γ-induced PARP14 auto-MARylation in CFPAC-1 cells. It inhibits IL-4-induced protumor M2-like macrophage polarization in isolated human primary macrophages. RBN-012759 (1 µM) also induces expression of the genes encoding the pro-inflammatory chemokines chemokine (C-C motif) ligand 13 (CCL13), CCL19, and chemokine (C-X-C motif) ligand 11 (CXCL11) in human kidney cancer tumor explants.
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1. A potent and selective PARP14 inhibitor decreases protumor macrophage gene expression and elicits inflammatory responses in tumor explants. Cell Chem. Biol. 28(8), 1158-1168.e1113 (2021).