PARP1-IN-61

PARP1-IN-61 (compound 33) is a potent PARP1 binder in the FP assay with an IC₅₀ of 13.03 nM and shows no activity against PARP3, PARP5a, or PARP6 up to 90000 nM^[1].
PARP1-IN-61 binds PARP1 with high affinity (SPR K_D 0.014 nM) and is selective over PARP2 (K_D >2000 nM); it also shows no significant hERG, Nav1.5, or Cav1.2 activity^[1].
PARP1-IN-61 inhibits PDE3A in enzymatic assays with an IC₅₀ of 1.5 μM^[1].
PARP1-IN-61 exhibits a CTG IC₅₀ of 2.0 nM in DLD-1 BRCA2 cells and no activity in DLD-1 WT cells; in MDA-MB-436 BRCA1-mutant cells, the CTG IC₅₀ is 2.4 nM and the IC₉₀ is 14 nM^[1].
PARP1-IN-61 potently inhibits PARylation in MDA-MB-436 cells with an IC₅₀ of 0.35 nM; it increases γH2AX in DLD-1 BRCA2 cells with an IC₅₀ of 18.0 nM^[1].
PARP1-IN-61 exhibits high Caco-2 permeability and low Caco-2 efflux with an ER of 1.4; it shows relatively high MDCK-MDR1 efflux but low MDCK-BCRP efflux (ER 0.85); and it has low intrinsic clearance in both human and rat hepatocytes^[1].