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Updated: Aug 15, 2026
An In Vitro Approach to Photodynamic Therapy
Published on: August 17, 2018
Light-Induced Structural Rearrangements of Axitinib and Their Role in Phototoxic Responses
Meryem El Ouardi1, Alejandro Álvarez1, Debora do Carmo Linhares2
1Departamento de Química-Instituto de Tecnología Química UPV-CSIC. Universitat Politècnica de València, Camino de Vera s/n, 46022, Valencia, Spain; Unidad Mixta de Investigación UPV-Instituto de Investigación Sanitaria (IIS) La Fe, Hospital Universitari i Politècnic La Fe, Avenida de Fernando Abril Martorell 106, 46026, Valencia, Spain.
Axitinib (AXT) phototoxicity arises from its (Z)-isomer, which forms in lipophilic environments and causes DNA damage upon light exposure. Understanding this isomerization is key for AXT-based light-modulated therapies.
Area of Science:
- Photochemistry
- Biochemistry
- Pharmacology
Background:
- Axitinib (AXT), a tyrosine kinase inhibitor, has a photoisomerizable scaffold explored in light-modulated therapies.
- The photobiological effects of AXT's light-induced structural changes are not well understood.
Purpose of the Study:
- To elucidate the mechanistic basis of Axitinib phototoxicity.
- To distinguish the phototoxic roles of its (E)- and (Z)-isomers.
- To link isomerization, microenvironmental stabilization, and photosensitization.
Main Methods:
- Photophysical characterization (steady-state photolysis, laser flash photolysis).
- Cellular studies in keratinocytes.
- Alkaline comet assays and γ-H2AX immunostaining.
Main Results:
- (E)-AXT isomerizes to (Z)-AXT in lipophilic environments and protein-rich media like HSA.
- (Z)-AXT is a phototoxic species, stabilized by HSA, causing protein oxidation and light-induced DNA double-strand breaks.
- Two phototoxic pathways involve (Z)-AXT formation and its intrinsic phototoxicity.
Conclusions:
- The (Z)-isomer of Axitinib is a significant phototoxic species.
- Microenvironmental factors, particularly protein binding, stabilize the phototoxic (Z)-AXT.
- A mechanism linking isomerization, stabilization, and Type I photosensitization is established for Axitinib.
