DR2313 is a competitive inhibitor of poly(ADP-ribose) polymerase (IC50: 0.20 and 0.24 μM for PARP-1 and PARP-2 respectively). It also has neuroprotective.

PARP2:0.24 μM, PARP1:0.20 μM

DR 2313 decreases neuronal cell death in models of cerebral ischemia in vivo and in vitro.

In both permanent and transient focal ischemia models in rats, pretreatment with DR2313 (10 mg/kg i.v. bolus and 10 mg/kg/h i.v. infusion for 6 h) significantly reduced the cortical infarct volume.?To determine the therapeutic time window of neuroprotection by DR2313, the effect of post-treatment was examined in transient focal ischemia model and compared with that of a free radical scavenger, MCI-186 (3-methyl-1-phenyl-2-pyrazolone-5-one).?Pretreatment with MCI-186 (3 mg/kg i.v. bolus and 3 mg/kg/h i.v. infusion for 6 h) significantly reduced the infarct volume, whereas the post-treatment failed to show any effects.?In contrast, post-treatment with DR2313 (same regimen) delaying for 2 h after ischemia still prevented the progression of infarction.?These results indicate that DR2313 exerts neuroprotective effects via its potent PARP inhibition, even when the treatment is initiated after ischemia.?Thus, a PARP inhibitor like DR2313 may be more useful in treating acute stroke than a free radical scavenger[1].