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ZFIN ID: ZDB-PUB-150825-52
A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos
Bliman, D., Nilsson, J.R., Kettunen, P., Andréasson, J., Grøtli, M.
Date: 2015
Source: Scientific Reports   5: 13109 (Journal)
Registered Authors: Kettunen, Petronella
Keywords: none
MeSH Terms:
  • Adenosine Triphosphate/metabolism
  • Animals
  • Binding Sites
  • Drug Design
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/embryology*
  • Humans
  • Light
  • Motor Neurons/drug effects*
  • Photolysis
  • Protein Kinase Inhibitors/chemical synthesis
  • Protein Kinase Inhibitors/chemistry
  • Protein Kinase Inhibitors/pharmacology*
  • Proto-Oncogene Proteins c-ret/antagonists & inhibitors*
  • Proto-Oncogene Proteins c-ret/metabolism
  • Zebrafish/embryology*
PubMed: 26300345 Full text @ Sci. Rep.
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.