Advancing Blue‐Light Photoactivatable TAM Kinase Inhibitors for Cancer Treatment: Challenges in Using π ‐Extended Coumarins as Photocleavable Protecting Groups
Abstract
This work presents the development of photocleavable tyrosine kinase inhibitors as a potential targeted cancer therapy. Focusing on the TAM family—Tyro3, Axl, and MERTK—overexpressed in several cancers (bladder, lung, and pancreas), we report the use of π-extended coumarins as photoremovable protecting groups to generate visible-light responsive photocleavable derivatives of the clinically relevant inhibitor UNC2025. This study highlights how the electronwithdrawing and donating groups in the π-extended coumarins affect both the photophysical properties of the photocaged UNC2025 and its biological activity in enzymatic and cellular assays, in terms of loss of inhibitory activity in absence of irradiation and recovery of UNC2025 activity following irradiation in the blue range. The most promising candidate was the N,O-dicaged compound bearing a π-extended coumarin with an electron-donating group.
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BibTeX
@article{billotte2026advancing,
title = {{Advancing Blue‐Light Photoactivatable TAM Kinase Inhibitors for Cancer Treatment: Challenges in Using π ‐Extended Coumarins as Photocleavable Protecting Groups}},
author = {Sébastien Billotte and Gaëlle Fontaine and Frédéric Bolze and Alexandre Specht and Sophie Bombard and Sandrine Piguel},
journal = {ChemPhotoChem},
year = {2026},
month = oct,
doi = {10.1002/cptc.70308},
url = {https://hal.science/hal-05828660v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Advancing Blue‐Light Photoactivatable TAM Kinase Inhibitors for Cancer Treatment: Challenges in Using π ‐Extended Coumarins as Photocleavable Protecting Groups
AU - Sébastien Billotte
AU - Gaëlle Fontaine
AU - Frédéric Bolze
AU - Alexandre Specht
AU - Sophie Bombard
AU - Sandrine Piguel
PY - 2026
DA - 2026/10/19
JO - ChemPhotoChem
DO - 10.1002/cptc.70308
UR - https://hal.science/hal-05828660v1
AB - This work presents the development of photocleavable tyrosine kinase inhibitors as a potential targeted cancer therapy. Focusing on the TAM family—Tyro3, Axl, and MERTK—overexpressed in several cancers (bladder, lung, and pancreas), we report the use of π-extended coumarins as photoremovable protecting groups to generate visible-light responsive photocleavable derivatives of the clinically relevant inhibitor UNC2025. This study highlights how the electronwithdrawing and donating groups in the π-extended coumarins affect both the photophysical properties of the photocaged UNC2025 and its biological activity in enzymatic and cellular assays, in terms of loss of inhibitory activity in absence of irradiation and recovery of UNC2025 activity following irradiation in the blue range. The most promising candidate was the N,O-dicaged compound bearing a π-extended coumarin with an electron-donating group.
SN - 2367-0932
ER -