PJ-34

Definition

ChEBI: PJ34 is a member of the class of phenanthridines that is 5,6-dihydrophenanthridine substituted at positions 2 and 6 by (N,N-dimethylglycyl)amino and oxo groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 of 110 nM and 86 nM, respectively) and exhibits anti-cancer, cardioprotective and neuroprotective properties. It has a role as an EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor, an antineoplastic agent, an apoptosis inducer, an angiogenesis inhibitor, an antiatherosclerotic agent, a cardioprotective agent, an anti-inflammatory agent and a neuroprotective agent. It is a member of phenanthridines, a secondary carboxamide and a tertiary amino compound. It is a conjugate base of a PJ34(1+).

Enzyme inhibitor

This PARP inhibitor (FWfree-base = 295.34 g/mol; FWhydrochloride = 331.80 g/mol), systematically named N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)- N,N-dimethylacetamide and known for its activity in neuroprotection under stress conditions, exclusively eradicates multi-centrosomal human mammary, colon, lung, pancreas, ovarian cancer cells, by acting as an extracentrosome extracentrosome( s) de-clustering agent in mitosis. When applied at 20-30 μM, PJ-34 caused G2/M-arrest and a massive cell death Normal human proliferating endothelial, epithelial and mesenchymal cells were unaffected. PJ-34’s cytotoxicity on cancer cells is not attributable to PARP inhibition alone. PJ-34 was originally designed to protect neuronal cells in the central nervous system from cell death evoked by high activity of PARP-1 in response to DNA damage caused by brain injury, stroke or inflammation. Targets: extra-centrosome de-clustering; polyADP-ribose polymerase-1, EC50 = 20 nM