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• W1991342634 endingPage "1996" @default.
• W1991342634 startingPage "1987" @default.
• W1991342634 abstract "K-252 compounds, which share a common polyaromatic aglycon structure, are rather general and potent inhibitors of various protein kinases, including protein kinase C and tyrosine-specific protein kinases, and possibly act by interfering at or near the ATP binding site. However, chemical modifications in their sugar moiety can result in high specificity of the inhibitory action and, furthermore, can induce other stimulatory and inhibitory effects on nerve cells. These compounds are of particular interest because, in intact cells, they inhibit the actions of NGF and other neurotrophins without diminishing comparable actions of other growth factors. This effect seems to reflect a direct inhibitory action on trk neurotrophin receptor proteins. At concentrations lower than those necessary to inhibit neurotrophin actions, K-252a and K-252b have been shown to potentiate the stimulatory effects of NT-3 on different neurons in culture and on PC12 cells. The structural requirements for this effect seem to be different from those for the inhibition of neurotrophin actions. These findings raise the possibility of development of compounds of high selectivity, able to inhibit or potentiate the transduction mechanisms of individual neurotrophins, and identify K-252a and K-252b as lead compounds for the development of such selective molecules. Specific inhibitors and stimulators of neurotrophins would be valuable tools to investigate biological functions of the neurotrophins in vitro and in vivo. Furthermore, it is possible that, in the future, highly selective drugs with agonistic or antagonistic actions on neurotrophin mechanisms could become therapeutically useful in the treatment of neurological disease and injury." @default.
• W1991342634 created "2016-06-24" @default.
• W1991342634 creator A5043191335 @default.
• W1991342634 creator A5054270816 @default.
• W1991342634 date "2006-10-05" @default.
• W1991342634 modified "2023-10-12" @default.
• W1991342634 title "K-252 Compounds: Modulators of Neurotrophin Signal Transduction" @default.
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• W1991342634 doi "https://doi.org/10.1111/j.1471-4159.1992.tb10085.x" @default.
• W1991342634 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1431889" @default.
• W1991342634 hasPublicationYear "2006" @default.
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