Kwang-Seok Oh, Sunkyung Lee, Kyu Yang Yi, Ho Won Seo, Hyun-Na Koo, and Byung Ho Lee

JPET/2008/143719 A novel and orally active poly (ADP-ribose) polymerase-1 inhibitor, 2- [methoxycarbonyl(4-methoxyphenyl)methyl sulfanyl]-1H-benzimidazole-4-carboxylic acid amide (KR-33889), attenuates injury in in vitro model of cell death and in vivo model of cardiac ischemia

Supplemental TABLE 1

Effects of KR-33889 on the alterations in mean arterial pressure and heart rate in rats subjected to 30 min occlusion of left anterior descending coronary artery followed by 3 h reperfusion.

Parameter Dose Baseline Occlusion Reperfusion (mg/kg) 30 min 1 h 2 h 3 h

MAP Vehicle 82.8±2.5 91.2±4.9 87.0±7.0 83.8±6.2 75.8±6.1 0.03 80.5±3.8 81.9±3.9 82.3±5.0 80.1±4.1 77.9±4.3 0.1 85.2±4.3 86.2±7.6 86.2±7.3 79.7±6.1 72.3±5.5 0.3 87.6±5.2 98.4±6.3 91.4±7.1 83.4±6.4 78.4±5.1 1.0 84.0±2.6 90.3±3.1 85.8±4.7 76.3±2.7 75.1±2.6 3.0 85.5±3.0 92.5±3.9 84.5±3.7 78.9±4.1 76.4±4.2 HR Vehicle 378±14 360±33 392±21 370±13 375±14 0.03 365±23 343±24 338±28 368±24 375±23 0.1 380±25 366±23 370±19 367±10 365±14 0.3 357±16 373±21 367±14 365±17 369±6 1.0 371±11 362±26 384±18 355±17 371±18 3.0 385±22 387±25 381±19 378±18 386±16 Drugs were given twice by i.v. bolus at first 5 min before occlusion and then at reperfusion. Values are mean ± S.E.M. (n=8-14). MAP, mean arterial pressure (mmHg);

HR, heart rate (beats/min). Supplemental TABLE 2

MAP Vehicle 82.8±2.5 91.2±4.9 87.0±7.0 83.8±6.2 75.8±6.1 0.1 81.5±2.7 90.7±3.3 88.0±4.2 81.9±2.3 78.2±2.7 1.0 78.5±3.9 88.0±5.2 89.2±5.6 79.0±3.2 76.2±4.6 HR Vehicle 378±14 360±33 392±21 370±13 375±14 0.1 378±15 400±16 397±12 361±30 393±24 1.0 352±25 326±10 337±6 351±13 340±13 Drugs were given twice by i.v. bolus at first 5 min before occlusion and then at reperfusion. Values are mean ± S.E.M. (n=8-10). MAP, mean arterial pressure (mmHg);

HR, heart rate (beats/min). Supplemental TABLE 3

Parameter Treatment Dose Baseline Occlusion Reperfusion (mg/kg) 30 min 1 h 2 h 3 h

MAP Both Vehicle 82.8±2.5 91.2±4.9 87.0±7.0 83.8±6.2 75.8±6.1 KR-33889 85.5±3.0 92.5±3.9 84.5±3.7 78.9±4.1 76.4±4.2 Pre-Isch Vehicle 78.3±3.6 84.3±4.2 82.4±4.7 73.2±4.0 69.3±3.7 KR-33889 82.1±3.2 84.6±3.9 84.6±3.7 79.3±3.8 75.1±3.6 With-Rep Vehicle 78.5±3.1 85.8±4.6 87.0±4.9 79.5±4.8 75.0±3.8 KR-33889 77.4±2.8 81.0±4.2 80.0±4.5 74.0±4.9 72.9±5.8 HR Both Vehicle 378±14 360±33 392±21 370±13 375±14 KR-33889 385±22 387±25 381±19 378±18 392±21 Pre-Isch Vehicle 391±27 392±26 394±23 378±21 388±24 KR-33889 390±3 366±18 373±3 384±13 379±4 With-Rep Vehicle 372±11 367±14 376±10 370±12 376±14 KR-33889 390±20 382±20 380±14 378±13 369±16 KR-33889 (3 mg/kg) were given by i.v. bolus at 5 min before occlusion (Pre-Isch), at reperfusion (With-Rep) or both (Both). Values are mean ± S.E.M. (n=7-9). MAP, mean arterial pressure (mmHg); HR, heart rate (beats/min). Supplemental TABLE 4

MAP Vehicle 82.5±4.0 89.5±4.3 85.4±4.3 80.6±4.9 73.8±5.4 1.0 79.4±5.0 85.1±5.0 84.7±3.9 78.9±4.1 76.0±5.0 10.0 77.9±3.5 82.7±4.5 82.3±5.2 78.1±5.7 75.6±6.0 HR Vehicle 402±11 390±15 377±19 369±7 377±9 1.0 387±22 381±15 389±17 377±19 379±15 10.0 367±12 368±15 379±17 375±26 383±16 Drugs were orally administered at 1 h before occlusion. Values are mean ± S.E.M. (n=6-

8). MAP, mean arterial pressure (mmHg); HR, heart rate (beats/min).