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Overview
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Background
Ki= 57 μM BGP-15 is a PARP inhibitor.As a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase(PARP), PARP inhibitors are considered a potential treatment for stroke and myocardial infarction.In vitro: Previous study showed that BGP-15 at 200 μM could prevent the imatinib-induced oxidative damages, attenuate the depletion of high-energy phosphates, alter the signaling effect of imatinib by preventing p38 MAP kinase and JNK activation, and also induce the Akt and GSK-3β phosphorylation [1]. In vivo: In-vivo study indicated that BGP-15 improved cardiac function and reduced arrhythmic episodes in two HF and AF mouse models. In these models, BGP-15 was associated with increased phosphorylation of IGF1R. Moreover, cardiac-specific IGF1R transgenic overexpression in mice recapitulated the protection caused by BGP-15. The authors further demonstrated that BGP-15 with IGF1R could provide protection independent of phosphoinositide 3-kinase-Akt and heat-shock protein 70 [2]. Clinical trial: A safety and efficacy of BGP-15 in patients with type 2 diabetes mellitus has been scheduled, however, this study is now terminated due to the funding support withdrawn. (https://clinicaltrials.gov/ct2/show/NCT01069965 term=BGP-15&rank=1)
[1] Sarszegi Z,Bognar E,Gaszner B,Kónyi A,Gallyas F Jr,Sumegi B,Berente Z. BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Mol Cell Biochem.2012 Jun;365(1-2):129-37.
[2] Sapra G,Tham YK,Cemerlang N,et al. The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice. Nat Commun.2014 Dec 9;5:5705.
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