Kraft, Fabian; Hanl, Maria; Feller, Felix; Schäker-Hübner, Linda; Hansen, Finn: Photocaged Histone Deacetylase Inhibitors as Prodrugs in Targeted Cancer Therapy. In: Pharmaceuticals. 2023, vol. 16, iss. 3, 1-16.
Online-Ausgabe in bonndoc:
author = {{Fabian Kraft} and {Maria Hanl} and {Felix Feller} and {Linda Schäker-Hübner} and {Finn Hansen}},
title = {Photocaged Histone Deacetylase Inhibitors as Prodrugs in Targeted Cancer Therapy},
publisher = {MDPI},
year = 2023,
month = feb,

journal = {Pharmaceuticals},
volume = 2023, vol. 16,
number = iss. 3,
pages = 1--16,
note = {Histone deacetylases (HDACs) play a key role in the control of transcription, cell prolifer- ation, and migration. FDA-approved histone deacetylase inhibitors (HDACi) demonstrate clinical efficacy in the treatment of different T-cell lymphomas and multiple myeloma. However, due to unselective inhibition, they display a wide range of adverse effects. One approach to avoiding off- target effects is the use of prodrugs enabling a controlled release of the inhibitor in the target tissue. Herein, we describe the synthesis and biological evaluation of HDACi prodrugs with photo-cleavable protecting groups masking the zinc-binding group of the established HDACi DDK137 (I) and VK1 (II). Initial decaging experiments confirmed that the photocaged HDACi pc-I could be deprotected to its parent inhibitor I. In HDAC inhibition assays, pc-I displayed only low inhibitory activity against HDAC1 and HDAC6. After irradiation with light, the inhibitory activity of pc-I strongly increased. Subsequent MTT viability assays, whole-cell HDAC inhibition assays, and immunoblot analysis confirmed the inactivity of pc-I at the cellular level. Upon irradiation, pc-I demonstrated pronounced HDAC inhibitory and antiproliferative activities which were comparable to the parent inhibitor I. Additionally, only phototreated pc-I was able to induce apoptosis in Annexin V/PI and caspase-Glo 3/7 assays, making pc-I a valuable tool for the development of light-activatable HDACi.},
url = {}

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