KMR-206 (KMR206) is a potent, selective PARP7 inhibitor with IC50 of 13.7 nM, displays 75-fold selectivity for PARP7 over PARP2 and does not inhibit PARP1 up to 3 uM.
KMR-206 is more than 50-fold selective for PARP7 over most PARP family members beyond PARP1 and PARP2, KMR-206 still exhibits an approximately 10-fold selectivity for PARP7 over MARylating PARPs (PARP10 and PARP11).
KMR-206 dose-dependently decreases PARP7 MARylation in GFP-PARP7-expressing HEK 293T cells with EC50 of 8 nM.
KMR-206 (100 nM) inhibits PARP7 catalytic activity and derepresses AHR ligand-mediated gene transcription in MEFs, stimulates IFN-β transcription and acts synergistically with 3pRNA and cGAMP.
KMR-206 (0.01-0.3 uM) increase STAT1 and phospho-Tyr701-STAT1 (pSTAT1) in a dose-dependent manner, induces an STING-dependent type I IFN response and PARP7 protein accumulation in CT-26 cells.
KMR-206 dose-dependently decreases the viability of NCI-H1373 cells with EC50 of 104 nM, increases PARP7 abundance in the nucleus in HiBiT-PARP7 knockin (KI) CT-26 cells.