EB 47 is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1; IC50 = 45 nM) and a dual site inhibitor of tankyrase 2 (TNKS2; IC50 = 45 nM).[1],[2] It also inhibits tankyrase 1 (TNKS1) and PARP10 (IC50s = 410 and 1,179 nM, respectively).2,3 EB 47 (10 mg/kg per hour) reduces infarct volume in a rat model of ischemia-reperfusion injury induced by middle cerebral artery occlusion (MCAO).[4]
References:
[1].Jagtap, P.G., Southan, G.J., Baloglu, E., et al.The discovery and synthesis of novel adenosine substituted 2,3-dihydro-1H-isoindol-1-ones: Potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)Bioorg. Med. Chem. Lett.14(1)81-85(2004).
[2].Haikarainen, T., Narwal, M., Joensuu, P., et al.Evaluation and structural basis for the inhibition of tankyrases by PARP inhibitorsACS Med. Chem. Lett.5(1)18-22(2013).
[3].Venkannagari, H., Fallarero, A., Feijs, K.L.H., et al.Activity-based assay for human mono-ADP-ribosyltransferases ARTD7/PARP15 and ARTD10/PARP10 aimed at screening and profiling inhibitorsEur. J. Pharm. Sci.49(2)148-156(2013).
[4].Ferraris, D.V.Evolution of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinicJ. Med. Chem.53(12)4561-4584(2010).