NU1025 (NSC-696807) is a potent PARP inhibitor with IC50 of 400 nM.

PARP:400 nM

NU1025 (0.2 mM) 处理减轻了 Water2 引起的细胞毒性。NU1025 本身对细胞活性没有任何影响。NU1025 预处理显著提高了 SIN-1 (0.8 mM) 处理细胞的活性（82.59±4.67%）。[2] NU1025 对 D54 和 U251 细胞的增殖没有可检测的影响。NU1025 处理显著抑制了 TPT 和 RT 处理诱导的 PARP-1 的增强活化。[3] 仅用 200 μM NU1025 处理后，未检测到 DNA 链断裂。[4]

使用NU1025（1和3 mg/kg）处理，与对照组大鼠相比，可将梗塞面积减少至25%和45%。NU1025（1和3 mg/kg）治疗显著减少了水肿体积。此外，NU1025还显著改善了神经功能缺损。[2]

PARP activation assay: Cells are suspended in hypotonic buffer (9 mM HEPES, pH 7.8, 4.5% (v/v) dextran, 4.5 mM MgCl2 and 5 mM DTT) at 1.5 × 107/mL on ice for 30 min, then 9 vol of isotonic buffer (40 mM HEPES, pH 7.8, 130 mM KCl, 4% (v/v) dextran, 2 mM EGTA, 2.3 mM MgCl2, 225 mM sucrose and 2.5 mM DTT) is added. The reaction is started by adding 300 μL cells to 100 μL 300 μM NAD+ containing [32P]-NAD+, and terminated by the addition of 2 mL ice-cold 10% (w/v) TCA +10% (w/v) sodium pyrophosphate. After 30 min on ice the precipitated 32P-labelled ADP-ribose polymers are filtered, washed five times with 1% (v/v) TCA, 1% (v/v) sodium pyrophosphate, dried and counted.

Cells are seeded in 96-well plates at a density of 2,500 cells/well and treated with the indicated doses of NU1025. Adherent cells are irradiated in medium with 250 kVp X-rays (dose rate 0.5 Gy/min). Untreated cells are used as a control. Following an up to 5 day incubation, cell proliferation is assessed by MTT assay.(Only for Reference)