RBN-012759 is an inhibitor of poly(ADP-ribose) polymerase 14 (PARP14; IC50 = 0.003 ?M).1 It is selective for PARP14 over PARP1-4, -5a, -5b, -6-12, -15, and -16 (IC50s = 1->100 ?M). RBN-012759 (10 ?M) 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 ?M) 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.
1.Schenkel, L.B., Molina, J.R., Swinger, K.K., et al.A potent and selective PARP14 inhibitor decreases protumor macrophage gene expression and elicits inflammatory responses in tumor explantsCell Chem. Biol.28(8)1158-1168.e1113(2021)