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• W2170504609 abstract "Proper management of prostate cancer patients is highly dependent on the spread of the disease. High expression levels of the androgen receptor (AR) in prostate tumor offer a target for identifying cancer metastasis. We investigated the use of nonsteroidal AR ligands for receptor-mediated imaging as a diagnostic tool for prostate cancer staging. Compound <i>S</i>-26 [<i>S</i>-3-(4-fluorophenoxy)-2-hydroxy-2-methyl-<i>N</i>-(4-cyano-3-iodophenyl)-propionamide]was identified from a series of iodinated ether-linked derivatives of bicalutamide due to its high-AR binding affinity of 3.3 nM (which is similar to testosterone and ∼25% of the binding affinity of dihydrotestosterone) in an in vitro competitive binding assay using rat prostate cytosol. Furthermore, <i>S</i>-26 exhibited a greater binding affinity (<i>K</i>_i = 4.4 nM) in a whole-cell binding assay using COS-7 cells transfected with human AR than testosterone (<i>K</i>_i = 32.9 nM) and dihydrotestosterone (<i>K</i>_i = 45.4 nM). We also confirmed that sex hormone-binding globulin (SHBG), a plasma protein that binds steroids with high affinity, does not bind with <i>S</i>-26. Cotransfection studies with the estrogen, progesterone, and glucocorticoid receptor indicated that <i>S</i>-26 does not cross-react with other members of the steroid hormone receptor family. The nonsteroidal structure, high-AR binding affinity, specificity, and lack of binding to SHBG indicate that <i>S</i>-26 exhibits favorable properties for further development as an imaging agent for prostate cancer." @default.
• W2170504609 created "2016-06-24" @default.
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• W2170504609 date "2006-01-24" @default.
• W2170504609 modified "2023-09-27" @default.
• W2170504609 title "Preclinical Pharmacology of a Nonsteroidal Ligand for Androgen Receptor-Mediated Imaging of Prostate Cancer" @default.
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• W2170504609 doi "https://doi.org/10.1124/jpet.105.094334" @default.
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