Orally available NO-mimicking free radical trapping agent and sulfatase 2 (SULF2) inhibitor with in vivo efficacy in animal models of glioma and stroke.
Originally characterized for its NO-mimicking activity in preventing peroxynitrite formation and in vivo neuroprotective efficacy in animal models of cerebral ischemia (100 mg/kg i.v. in rabbits; 30-60 mg/kg plus 30-60 mg/kg/h i.v. or 50 mg/kg plus 8.8 mg/kg/h s.c. in rats; 28 mg/kg plus 16 mg/kg/h i.v. in monkeys), OKN-007 (HPN-07, NXY-059) is an orally available α-phenyl-tert-butylnitrone (PBN) derivative that is also shown to exhibit sulfatase 2 (SULF2) inhibitory activity and anticancer efficacy both in cultures (effective conc. 170-200 μM in Huh7 heptoma cultures) and in several rodent glioma models in vivo (C6, RG2, and GL261; 75 mg/kg/day for rats and 168 mg/kg/day for mice via drinking water).
It has been proposed that the novel spin trap agent disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) may be useful in the treatment of ischemia and stroke. To date, there is little information concerning the safety of NXY-059 when administered in combination with the
Journal of magnetic resonance imaging : JMRI, 31(4), 796-806 (2010-04-08)
To demonstrate that OKN007, a disulfonyl derivative of phenyl-tert-butyl nitrone (PBN), has anti-glioma activity in the clinically relevant C6 rat glioma model using multi-parametric magnetic resonance imaging. Twenty-one rats were intracerebrally implanted with C6 cells and administered OKN007 or kept
Because free radical mechanisms may contribute to brain injury in hemorrhagic stroke, the effect of the free radical trapping agent disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) was investigated on outcome following intracerebral hemorrhage (ICH) in rat. ICH was induced in 20 adult
Free radicals have gained wide acceptance as mediators of cerebral ischemic injury. It has previously been reported that a spin trap nitrone, alpha-phenyl-N-tert-butyl nitrone (PBN), can reduce infarct volumes in rats subjected to either permanent or transient focal cerebral ischemia.
NXY-059 is a novel nitrone with free radical-trapping properties that has a considerable neuroprotective effect in rats. We have now examined the efficacy of this drug at reducing long-term functional disability in a primate model of stroke. Twelve monkeys were
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