BGP-15 (BGP-15 2HCl) is a PARP inhibitor with protecting effect after ischemia-reperfusion injury.

PARP:120 μM

在两种小鼠模型（将分步发展为心衰和房颤）中,BGP-15可改善心脏功能和减少心率不齐[2].在cisplatin处理前以 BGP-15（100-200 mg/kg,p.o.）处理可阻止或显著抑制cisplatin诱导的急性肾功能衰竭的发展.在cisplatin诱导的肾毒性中,BGP-15对肾脏的抗氧化反应具有显著作用.尽管BGP-15可使肾脏免受肾毒性,但它对细胞生长抑制剂的抗肿瘤效果没有减弱作用.在肾脏,BGP-15可抑制cisplatin诱导的二磷酸腺苷核糖多聚化[1].

BGP-15是HSP72的体外诱导物,但仅当与热激共同处理时有效,且不影响HSP90的水平[3]。BGP-15 (200 μM)可使高能磷酸化合物的损耗减弱,并防止imatinib mesylate诱导的氧化性损伤,这是通过诱导Akt和GSK-3beta的磷酸化、阻止p38 MAPK和JNK的激活改变imatinib mesylate的信号通路效应实现的。BGP-15可明显抑制p38和JNK的激活效应,因为在离体灌注心脏中这些激酶可促进细胞死亡和炎症反应[4]。

Human tumor cell lines A549, HCT-15, HCT-116, and Du-145 were maintained in RPMI 1640 medium supplemented with 10% FCS in humidified air containing 5% CO2. For in vitro cytotoxicity assays, 5×103 to 5×104 cells were plated into the wells of 96-well plates in 100 μL culture medium. On the following day, cells were exposed to BGP-15 (10, 30, 100 μg/mL) and to a series of concentrations of cisplatin either by itself or in combination. Cultures were incubated in a total volume of 200 μL for 3 more days at 37°. Samples were prepared in duplicates or triplicates. Cell growth was evaluated by MTT or SRB assays. Growth inhibition curves were calculated. (Only for Reference)