Retinal toxicity induced by small-molecule Hsp90 inhibitors in beagle dogs
نویسندگان
چکیده
منابع مشابه
A novel class of small molecule inhibitors of Hsp90.
Unregulated cellular proliferation, caused by mutation or dysregulation of growth-promoting proteins, is an underlying cause of cancer. Many such growth-promoting proteins exhibit an increased dependence on the activity of the chaperone heat-shock protein 90 (Hsp90) for correct folding and maturation in the cell. One can therefore envision that inhibition of Hsp90 would be an effective and broa...
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Three adult Beagle dogs given pyridoxine hydrochloride orally at a dose of 150 mg/kg body weight/day for about 100 days developed ataxia and had spastic, dysmetric leg movements. Ultrastructural alterations in the dorsal funiculus of the spinal cord were degeneration and loss of axons and myelin, and secondary changes of the myelin sheaths. Possible pathogenic mechanisms of pyridoxine neurotoxi...
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In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular e...
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ژورنال
عنوان ژورنال: The Journal of Toxicological Sciences
سال: 2014
ISSN: 0388-1350,1880-3989
DOI: 10.2131/jts.39.59