| Identification | Back Directory | [Name]
PJ-34 | [CAS]
344458-19-1 | [Synonyms]
PJ-34
CS-856
PJ34(free base)
PJ34;PJ-34;PJ 34
2-(dimethylamino)-N-(6-oxo-5H-phenanthridin-2-yl)acetamide
N,N-Dimethyl-2-(6-oxo-5,6-dihydrophenanthridin-2-yl)acetamide
N-(6-OXO-5,6-DIHYDRO-PHENANTHRIDIN-2-YL)-N,N-DIMETHYLACETAMIDE HCL
2-(dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl)acetamide
Acetamide, N-(5,6-dihydro-6-oxo-2-phenanthridinyl)-2-(dimethylamino)-
N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetamide
N-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)-N,N-DIMETHYLACETAMIDE HYDROCHLORIDE
N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetamide
PJ 34 | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C17H17N3O2 | [MDL Number]
MFCD03452993 | [MOL File]
344458-19-1.mol | [Molecular Weight]
295.34 |
| Hazard Information | Back Directory | [Uses]
PJ34 is a potent specific inhibitor of PARPl/2 with IC50 of 110 nM and 86 nM, respectively. | [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 | [in vivo]
To compare the potency and efficacy with other PARP inhibitors, PJ34 is evaluated at the doses of 3.2 and 10 mg/kg, respectively. PJ34 at the dose of 3.2 mg/kg significantly reduces cortical damage by 33%; however, 10 mg/kg dosing shows reversed effect (17% reduction)[1]. PJ34 (25 mg/kg) reduces the levels of TNF-α mRNA in ischemic animals by 70% and these values in treated mice do not differ from that of sham or naive animals. Treatment of ischemic mice with PJ34 reduces the level of E-selectin mRNA by 81% and that of ICAM-1 mRNA by 54%, compared to vehicle-treated ischemic mice[2]. | [IC 50]
PARP: 110 nM (IC50); PARP-2: 86 nM (IC50); PARP-1: 110 nM (IC50) | [storage]
Store at -20°C | [References]
[1] Iwashita A, et al. A novel and potent poly(ADP-ribose) polymerase-1 inhibitor, FR247304 (5-chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone), attenuates neuronal damage in in vitro and in vivo models of cerebral ischemia. J Ph DOI:10.1124/jpet.104.066944
[2] Haddad M, et al. Anti-inflammatory effects of PJ34, a poly(ADP-ribose) polymerase inhibitor, in transient focal cerebral ischemia in mice. Br J Pharmacol. 2006 Sep;149(1):23-30. DOI:10.1038/sj.bjp.0706837 |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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