Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223049
Title: Photoswitchable diazocine derivative for adenosine A3 receptor activation in psoriasis
Author: Tosh, Diliip K.
López-Cano, Marc
Scortichini, Mirko
Salmaso, Veronica
Ko, Tongil
Salort, Glòria
Filgaira Enri, Ingrid
Soler Prat, Concepció
Trauner, Dirk
Hernando, Jordi
Jacobson, Kenneth A.
Ciruela Alférez, Francisco
Keywords: Adenosina
Inflamació
Psoriasi
Adenosine
Inflammation
Psoriasis
Issue Date: 8-Jan-2025
Publisher: American Chemical Society
Abstract: Incorporating photoisomerizable moieties within drugs offers the possibility of rapid and reversible light-dependent switching between active and inactive configurations. Here, we developed a photoswitchable adenosine A3 receptor (A3R) agonist that confers optical control on this G protein-coupled receptor through noninvasive topical skin irradiation in an animal model of psoriasis. This was achieved by covalently bonding an adenosine-5′-methyluronamide moiety to a diazocine photochrome, whose singular photoswitching properties facilitated repeated interconversion between a thermally stable, biologically inactive Z agonist form and a photoinduced, pharmacologically active E configuration. As a result, our photoswitchable agonist allowed the precise modulation of A3R function both in vitro and in vivo, which led to a clear light-controlled pharmacotherapeutic effect on mouse skin lesions. This breakthrough not only demonstrates the potential of diazocine photoswitches for in vivo photopharmacology but also paves the way for the development of new strategies for skin-related diseases that require localized and temporally controlled drug action.
Note: Reproducció del document publicat a: https://doi.org/10.1021/jacs.4c13558
It is part of: Journal of the American Chemical Society, 2025, vol. 147, num.1, p. 874-879
URI: https://hdl.handle.net/2445/223049
Related resource: https://doi.org/10.1021/jacs.4c13558
ISSN: 0002-7863
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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