6(5H)-Phenanthridinone

6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 (EC50s = 10.2 and 36.3 μM, respectively, in yeast cells expressing the human enzymes).1 It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells when used at a concentration of 50 μM.2 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes.3 In vivo, 6(5H)-phenanthridinone (60 mg/kg) reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipid peroxidation, oxidative DNA damage, and PARP levels in a mouse model of carbon tetrachloride-induced hepatotoxicity when administered at a dose of 10 mg/kg.4

|1. Perkins, E., Sun, D., Nguyen, A., et al. Novel inhibitors of poly(ADP-ribose) polymerase/PARP1 and PARP2 identified using a cell-based screen in yeast. Cancer Res. 61(10), 4175-4183 (2001).|2. Weltin, D., Holl, V., Hyun, J.W., et al. Effect of 6(5H)-phenanthridinone, a poly (ADP-ribose)polymerase inhibitor, and ionizing radiation on the growth of cultured lymphoma cells. Int. J. Radiat. Biol. 72(6), 685-692 (1997).|3. Chiarugi, A. Inhibitors of poly(ADP-ribose) polymerase-1 suppress transcriptional activation in lymphocytes and ameliorate autoimmune encephalomyelitis in rats. Br. J. Pharmacol. 137(6), 761-770 (2002).|4. Banasik, M., Stedeford, T., Strosznajder, R.P., et al. Inhibition of poly(ADP-ribose) polymerase-1 attenuates the toxicity of carbon tetrachloride. J. Enzyme Inhib. Med. Chem. 26(6), 883-889 (2011).