Photoactivatable Small-Molecule Inhibitors for Light-Controlled TAM Kinase Activity
Julie Le Bescont
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorDr. Liliane Mouawad
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorDr. Thomas Boddaert
Université Paris-Saclay, CNRS UMR 8182 ICMMO, CP3A Organic Synthesis Group, 91405 Orsay, France
Search for more papers by this authorDr. Sophie Bombard
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorCorresponding Author
Dr. Sandrine Piguel
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorJulie Le Bescont
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorDr. Liliane Mouawad
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorDr. Thomas Boddaert
Université Paris-Saclay, CNRS UMR 8182 ICMMO, CP3A Organic Synthesis Group, 91405 Orsay, France
Search for more papers by this authorDr. Sophie Bombard
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorCorresponding Author
Dr. Sandrine Piguel
Institut Curie, Université PSL, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Université Paris-Saclay, CNRS UMR 9187, INSERM U1196 Chimie et Modélisation pour la Biologie du Cancer, 91405 Orsay, France
Search for more papers by this authorGraphical Abstract
TAM-light: The design, synthesis, photocleavage properties and inhibitory activities of the first four photoactivatable small molecules for controlling TAM kinase activity with light are reported.
Abstract
The TAM kinase family arises as a promising therapeutic target for cancer therapy, as well as auto-immune and viral diseases. In this study, we report the first photoactivatable caged inhibitors of Tyro3 and Mer. This strategy enables spatial and temporal control of the biological activity of the inhibitor upon irradiation with UV light. We describe the design, synthesis, photocleavage properties, and inhibitory activities of four Tyro3 and Mer photoactivatable small molecules. The proof of concept on the TAM kinase family was achieved in vitro, since irradiation by UV light restored the full inhibitory activity of two prodrugs.
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