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Effects of a newly developed tricyclic PARP‐1 inhibitor, on ischemic stroke
Author(s) -
Yoo A. Rum,
Koh SeongHo,
Noh Min Young,
Cho Goang Won,
Park JiSeon,
Kim Youngchul,
Lee HanChang,
Kim MyungHwa,
Kim Seung Hyun
Publication year - 2010
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20368
Subject(s) - poly adp ribose polymerase , tricyclic , stroke (engine) , pharmacology , parp inhibitor , ischemic stroke , medicine , enzyme , ischemia , chemistry , polymerase , biochemistry , mechanical engineering , engineering
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 (IC 50 =7.8 nM in an enzyme‐based assay and=0.73 µM 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. Drug Dev Res 71: 253–260, 2010. © 2010 Wiley‐Liss, Inc.