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A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos

Journal article
Authors David Bliman
Jesper Nilsson
Petronella Kettunen
Joakim Andréasson
Morten Grøtli
Published in Scientific Reports
Volume 5
Pages artikel nr 13109
ISSN 2045-2322
Publication year 2015
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Department of Chemistry and Molecular Biology
Pages artikel nr 13109
Language en
Links dx.doi.org/10.1038/srep13109
https://gup.ub.gu.se/file/203309
Subject categories Chemical Sciences, Biological Sciences

Abstract

Proto-oncogene tyrosine-protein kinase receptor RET is implicated in the development and maintenance of neurons of the central and peripheral nervous systems. Attaching activity-compromising photocleavable groups (caging) to inhibitors could allow for external spatiotemporally controlled inhibition using light, potentially providing novel information on how these kinase receptors are involved in cellular processes. Here, caged RET inhibitors were obtained from 3-substituted pyrazolopyrimidine-based compounds by attaching photolabile groups to the exocyclic amino function. The most promising compound displayed excellent inhibitory effect in cell-free, as well as live-cell assays upon decaging. Furthermore, inhibition could be efficiently activated with light in vivo in zebrafish embryos and was shown to effect motoneuron development.

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