Natural product–drug conjugates for modulation of TRPV1-expressing tumors |
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Institution: | 1. Department of Cardiology, Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal;2. Cardiovascular R&D Unit, Department of physiology and cardiothoracic surgery of Medical School of Porto, Portugal;3. Department of Cardiology, Hospital do Divino Espirito Santo, Ponta Delgada, Portugal |
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Abstract: | We report the design, synthesis and biological evaluation of natural product–drug conjugates for treatment of prostate cancers over-expressing the transient receptor potential vanilloid 1 (TRPV1) channel. We validate the relevance of TRPV1 as a target in prostate cancer patients by using a bioinformatics approach and provide proof-of-concept for the drug delivery strategy through bioorthogonal chemistry and stability assays under simulated physiological conditions. In cell-based assays, the constructs displayed modest activity. Moreover, we serendipitously discover that a stoichiometric combination of a TRPV1 agonist with a small, positively charged cytotoxic may provide new research avenues in personalized medicines for prostate cancer. |
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Keywords: | Small molecule–drug conjugates Cancer Drug delivery Chemical biology Ligand-gated ion channel |
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