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

PARP:120 μM

In two mouse models developed to exhibit heart failure and atrial fibrillation, BGP-15 has been shown to enhance cardiac function and reduce arrhythmia [2]. Pretreatment with BGP-15 (100-200 mg/kg, p.o.) before cisplatin administration can either prevent or significantly inhibit the development of cisplatin-induced acute renal failure. BGP-15 demonstrates significant antioxidant effects on the kidneys in the context of cisplatin-induced nephrotoxicity. Despite BGP-15's ability to protect the kidneys from nephrotoxic effects, it does not diminish the antitumor efficacy of cytostatic agents. In the kidneys, BGP-15 inhibits cisplatin-induced poly(ADP-ribose) polymerization [1].

BGP-15 acts as an in vitro inducer of HSP72, effective only when co-treated with heat shock, without affecting HSP90 levels. At a concentration of 200 μM, BGP-15 mitigates the depletion of high-energy phosphate compounds and prevents oxidative damage induced by imatinib mesylate. This is achieved by promoting the phosphorylation of Akt and GSK-3beta, and inhibiting the activation of p38 MAPK and JNK, thereby altering the signaling effects of imatinib mesylate. Moreover, BGP-15 significantly inhibits the activation of p38 and JNK, enzymes known to facilitate cell death and inflammatory responses in ex vivo perfused hearts.

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)