Effects of a newly developed tricyclic PARP-1 inhibitor, on ischemic stroke

✍ Scribed by A. Rum Yoo; Seong-Ho Koh; Min Young Noh; Goang Won Cho; Ji-Seon Park; Youngchul Kim; Han-Chang Lee; Myung-Hwa Kim; Seung Hyun Kim

• Book ID: 102145565
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 220 KB
• Volume: 71
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.20368

✦ Synopsis

Abstract

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.