title: A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos.
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.
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
authors: David
authors: D
authors: Bliman
authors: Department of Chemistry and Chemical Engineering, Physical Chemistry, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors: Jesper R
authors: JR
authors: Nilsson
authors: Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden.
authors: Petronella
authors: P
authors: Kettunen
authors: Department of Chemistry and Chemical Engineering, Physical Chemistry, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors: Joakim
authors: J
authors: Andréasson
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
authors: Morten
authors: M
authors: Grøtli
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology*; D006801:Humans; D008027:Light; D009046:Motor Neurons / Q000187:drug effects*; D010782:Photolysis; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*
chemical_list: C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D000255:Adenosine Triphosphate; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human