Disease relevance of NU1

• No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, NU1025, or hydrogen peroxide [1].
• Results of this study demonstrate the neuroprotective activity of NU1025 and suggest its potential in cerebral ischemia [2].
• We investigated the effects of combined treatments with the DNA topoisomerase I inhibitor Topotecan and the poly(ADPR)polymerase-1 inhibitor NU1025 in D54(p53wt) and U251(p53mut) glioblastoma cell lines [3].

High impact information on NU1

• The potentiation of growth inhibition by NU1025 and NU1085 varied between the cell lines from 1.5- to 4-fold for TM and 1- to 5-fold for TP and was unaffected by p53 status [4].
• In studies with L1210 cells in vitro, a concentration of 200 microM 8-hydroxy-2-methylquinazolinone (6, NU1025) (IC50 value 0.40 microM) potentiated the cytotoxicity of the monomethylating agent 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide and gamma-radiation 3.5- and 1.4-fold, respectively, at the 10% survival level [5].
• Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro [6].
• The potent novel poly(ADP-ribose) polymerase (PARP) inhibitor, NU1025, enhances the cytotoxicity of DNA-methylating agents and ionizing radiation by inhibiting DNA repair [6].
• Taken together, these data suggest that potentiation of camptothecin cytotoxicity by NU1025 is a direct result of increased DNA strand breakage, and that activation of PARP by camptothecin-induced DNA damage contributes to its repair and consequently cell survival [6].

Chemical compound and disease context of NU1

• In the present study we have evaluated the effects of PARP inhibitor, 8-hydroxy-2 methyl-quinazolin-4-[3H]one (NU1025) in H(2)O(2) and 3-morphilinosyndonimine (SIN-1) induced cytotoxicity in PC12 cells as well as in middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia in rats [2].

Biological context of NU1

• Investigation of DNA strand breakage and repair in gamma-irradiated cells by alkaline elution demonstrated that NU1025 caused a marked retardation of DNA repair [7].
• Neuroprotection with NU1025 was associated with reduction in PAR accumulation, reversal of brain NAD depletion and reduction in DNA fragmentation [2].
• Analysis of cell growth and cell cycle kinetics showed a synergistic anti-proliferative effect of 10nM TPT and 10muM NU1025 and a G(2)/M block of the cell cycle [3].
• Conversely, in U251(p53mut) cells we found that NU1025 incremented the TPT-dependent apoptosis characterised by PARP-1 proteolysis [3].

Associations of NU1 with other chemical compounds

• Pretreatment with NU1025 (0.2 mM) restored cell viability to approximately 73 and 82% in H(2)O(2) and SIN-1 injured cells, respectively [2].
• It has recently been suggested that our results might be limited to certain BRCA2 mutations as the CAPAN-1 cell line, which carries a naturally occurring 6174delT mutation in one BRCA2 allele accompanied by loss of the wild-type allele, is apparently insensitive to two PARP inhibitors 3-aminobenzamide (IC50 33 microM) and NU1025 (IC50 400 nM) [8].

Gene context of NU1

• There were no significant changes in NMNAT activity in response to MNNG treatment over 24 h, either in the presence or in the absence of NU1025 [9].

Analytical, diagnostic and therapeutic context of NU1

• NU1025 at 1 and 3 mg/kg reduced total infarct volume to 25% and 45%, respectively, when administered 1 h before reperfusion [2].

References