Effects of a Newly Developed Tricyclic PARP-1 Inhibitor, on Ischemic Stroke

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초록

Poly(ADP-ribose) polymerase (PARP)-1 plays an important role in the pathogenic mechanism of ischemic stroke. A number of studies have been undertaken to develop PARP-1 inhibitors for clinical use. We report on the newly developed PARP-1 inhibitors, among which 12a showed good activity (IC50) = 7.8 nM in an enzyme-based assay and = 0.73 mu M in a cell-based assay) and pharmacokinetic profiles. Treatment of the middle cerebral artery (MCA) occluded rats with 3 mg/kg 12a reduced infarct volume suggesting that, may be a good candidate for the treatment of ischemic stroke.

키워드

PARPinhibitorstrokePOLY(ADP-RIBOSE) SYNTHETASE ACTIVATIONCELL-DEATHBIOLOGICAL EVALUATIONCEREBRAL-ISCHEMIADNA-DAMAGEPOLYMERASE-1INFLAMMATIONDESIGNPOTENTPEROXYNITRITE
제목
Effects of a Newly Developed Tricyclic PARP-1 Inhibitor, on Ischemic Stroke
저자
Yoo, A. RumKoh, Seong-HoNoh, Min YoungCho, Goang WonPark, Ji-SeonKim, YoungchulLee, Han-ChangKim, Myung-HwaKim, Seung Hyun
DOI
10.1002/ddr.20368
발행일
2010-06
유형
Article
저널명
Drug Development Research
71
4
페이지
253 ~ 260