NU1025

Names

[ Name ]:
NU1025

[Synonym ]:
8-Hydroxy-2-methylquinazolin-4(1H)-one
2-methylquinazoline-4,8-diol
MFCD00942555
4,8-quinazolinediol, 2-methyl-
8-hydroxy-2-methyl-1H-quinazolin-4-one
8-hydroxy-2-methylquinazolin-4(3H)-one
8-Hydroxy-2-methyl-4(1H)-quinazolinone
4(1H)-Quinazolinone, 8-hydroxy-2-methyl-
8-Hydroxy-2-methyl-4(3H)-quinazolinone

Biological Activity

[Description]:

NU1025 is a potent PARP inhibitor with an IC50 of 400 nM and a Ki of 48 nM. NU1025 potentiates the cytotoxicity of ionizing radiation and anticancer drugs. NU1025 has anti-cancer and neuroprotective activity[1][2][3].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> PARP

Research Areas >> Neurological Disease

Signaling Pathways >> Cell Cycle/DNA Damage >> PARP

[Target]

IC50: 400 nM (PARP)[2] Ki: 48 nM (PARP)[3]

[In Vitro]

NU1025 (0.2 mM) pretreatment restores cell viability to approximately 73% and 82% in H2O2 and SIN-1 injured cells, respectively[1]. NU1025 enhances the cytotoxicity of the DNA-methylating agent MTIC, γ-irradiation and bleomycin 3.5-, 1.4- and 2-fold respectively in L1210 cells. The recovery from potentially lethal γ-irradiation damage cytotoxicity in plateau-phase cells is also inhibited by NU 1025. NU1025 causes a marked retardation of DNA repair[2]. Cell Viability Assay[1] Cell Line: PC12 cells Concentration: 0.2 mM Incubation Time: 6.5 hours Result: Restored cell viability to approximately 73% and 82% in H2O2 and SIN-1 injured cells.

[In Vivo]

NU1025 (1-3 mg/kg; intraperitoneal injection; male Sprague Dawley rats) treatment at 1 and 3 mg/kg reduces total infarct volume to 25% and 45%, respectively, when administered 1 h before reperfusion. NU1025 also produces significant improvement in neurological deficits. Neuroprotection with NU1025 is associated with reduction in PAR accumulation, reversal of brain NAD depletion and reduction in DNA fragmentation[1]. Animal Model: Male Sprague Dawley rats (250-270 g) induced focal cerebral ischemia[1] Dosage: 1 mg/kg, 3 mg/kg Administration: Intraperitoneal injection Result: At 1 and 3 mg/kg, reduced total infarct volume to 25% and 45%, respectively.

[References]

[1]. Kaundal RK, et al. Neuroprotective effects of NU1025, a PARP inhibitor in cerebral ischemia are mediated through reduction in NAD depletion and DNA fragmentation. Life Sci. 2006 Nov 10;79(24):2293-302.

[2]. Bowman KJ, et al. Potentiation of anti-cancer agent cytotoxicity by the potent poly(ADP-ribose) polymerase inhibitors NU1025 and NU1064. Br J Cancer. 1998 Nov;78(10):1269-77.

[3]. Delaney CA, et al. Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines. Clin Cancer Res. 2000 Jul;6(7):2860-7.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
345.4±44.0 °C at 760 mmHg

[ Melting Point ]:
253-258ºC

[ Molecular Formula ]:
C₉H₈N₂O₂

[ Molecular Weight ]:
176.172

[ Flash Point ]:
162.7±28.4 °C

[ Exact Mass ]:
176.058578

[ PSA ]:
65.98000

[ LogP ]:
0.35

[ Appearance of Characters ]:
solid | off-white

[ Vapour Pressure ]:
0.0±0.8 mmHg at 25°C

[ Index of Refraction ]:
1.678

[ Storage condition ]:
−20°C

[ Water Solubility ]:
DMSO: 35 mg/mL, soluble

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H319

[ Precautionary Statements ]:
P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
22

[ Safety Phrases ]:
26

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Rapamycin-resistant poly (ADP-ribose) polymerase-1 overexpression is a potential therapeutic target in lymphangioleiomyomatosis.

Am. J. Respir. Cell. Mol. Biol. 51(6) , 738-49, (2014)

Lymphangioleiomyomatosis (LAM) is a female-predominant cystic lung disease that can lead to respiratory failure. LAM cells typically have inactivating tuberous sclerosis complex 2 (TSC2) mutations and...

Related Compounds

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