Volume 5, Issue 11 pp. 989-994
Communication

Photoactivatable Small-Molecule Inhibitors for Light-Controlled TAM Kinase Activity

Julie Le Bescont

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

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Dr. Liliane Mouawad

Dr. 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

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Dr. Thomas Boddaert

Dr. Thomas Boddaert

Université Paris-Saclay, CNRS UMR 8182 ICMMO, CP3A Organic Synthesis Group, 91405 Orsay, France

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Dr. Sophie Bombard

Dr. 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

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Dr. Sandrine Piguel

Corresponding 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

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First published: 29 June 2021
Citations: 3

Graphical 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.