Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 59, Issue 21, Pages 9974-9980Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01426
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Funding
- Alfonso Martin Escudero Foundation
- EC [H2020-MSCA-IF-2014-658833]
- EPSRC [EP/N021134/1]
- EPSRC [EP/N021134/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/N021134/1] Funding Source: researchfish
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Bioorthogonal uncaging strategies have recently emerged as an experimental therapeutic approach to control drug release. Herein we report a novel masking strategy that enables to modulate the metal chelating properties of hydroxamic acid groups by bioorthogonal chemistry using Pd-functionalized resins. This novel approach allowed to devise an inactive precursor of the histone deacetylase inhibitor vorinostat that was efficiently uncaged by heterogeneous Pd catalysis in cell culture models of glioma and lung cancer.
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