Research Area
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Description
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Neurological Disease |
Biological Activity
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Description
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NXY-059 (Cerovive) is a novel nitrone, shows efficacious neuroprotective effects. |
Targets
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IC50 |
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In Vitro
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NXY-059 is more soluble than the spin trapping agent α-phenyl-N-tert-butyl nitrone (PBN). [1] In an in vitro blood-brain barrier (BBB) model, 250 mM of NXY-059 administered at the onset or up to 4 h after oxygen glucose deprivation (OGD) produces a significant reduction in the increased BBB permeability caused by OGD. Furthermore, OGD produces a huge influx of tissue plasminogen activator across the BBB, which is substantially reduced by NXY-059. [2] |
In Vivo
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NXY-059 reduces infarct volume in rats subjected to 2 hours of middle cerebral artery occlusion in a dose-dependent manner. At equimolar doses (3.0 mg/kg for NXY-059 and 1.4 mg/kg for PBN), NXY-059 is more efficacious than PBN. Similar results are obtained when a recovery period of 7 days is allowed. The window of therapeutic opportunity for NXY-059 is 3 to 6 hours after the start of recirculation. [1] NXY-059, a free radical-trapping agent, has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species. NXY-059 treatment reduces the overall amount of brain damage by >50% of saline-treatment values, with similar levels of protection afforded to both white and gray matter. [3] Treatment with NXY-059 (50 mg/kg subcutaneous plus 8.8 mg/kg/h for 3 days subcutaneous delivered via implanted osmotic pumps) significantly decreases neurological impairment following intracerebral hemorrhage in rat, and reduces the neutrophil infiltrate observed 48 hours post-hemorrhage in the vicinity of the hematoma, and the number of TUNEL-positive cells 48 hours post-hemorrhage at the hematoma margin. [4] |
Clinical Trials
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NXY-059 is now under the Phase 2 clinical trial in patients with prelapsed or refractory multiple myeloma. |
Features
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Combination Therapy
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Description
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NXY-059, combined with Bortezomib plus Dexamethasone, is now under the Phase 1 clinical trial in patients with prelapsed or refractory multiple myeloma. |
Protocol
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Animal Study
[1]
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Animal Models |
Monofilament fishing line is used to produce occlusion and neurologic deficit in male Wistar rats |
Formulation |
NXY-059 is dissolved in physiological saline. |
Doses |
0.3, 3.0 or 30 mg/kg |
Administration |
Administered into the right jugular vein. |
References |
[1] Kuroda S, et al, J Cereb Blood Flow Metab, 1999, 19(7), 778-787.
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[2] Culot M, et al, Brain Res, 2009, 19(1294), 144-152.
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[3] Marshall JW, et al, Stroke, 2001, 32(1), 190-198.
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[4] Peeling J, et al, Neuropharmacology, 2001, 40(3), 433-439.
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