PUBLICATION
A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos
- Authors
- Bliman, D., Nilsson, J.R., Kettunen, P., Andréasson, J., Grøtli, M.
- ID
- ZDB-PUB-150825-52
- 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.
Citation
Bliman, D., Nilsson, J.R., Kettunen, P., Andréasson, J., Grøtli, M. (2015) A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos. Scientific Reports. 5:13109.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping