nonsteroidal ligand for androgen receptor

xtraflossy

xtraflossy

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This sounded interesting.


Preclinical pharmacology of a nonsteroidal ligand for androgen receptor-mediated imaging of prostate cancer.

Yang J, Bohl CE, Nair VA, Mustafa SM, Hong SS, Miller DD, Dalton JT.

Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, USA.

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 S-26 [S-3-(4-fluorophenoxy)-2-hydroxy-2-methyl-N-(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 approximately 25% of the binding affinity of dihydrotestosterone) in an in vitro competitive binding assay using rat prostate cytosol. Furthermore, S-26 exhibited a greater binding affinity (K(i) = 4.4 nM) in a whole-cell binding assay using COS-7 cells transfected with human AR than testosterone (K(i) = 32.9 nM) and dihydrotestosterone (K(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 S-26. Cotransfection studies with the estrogen, progesterone, and glucocorticoid receptor indicated that S-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 S-26 exhibits favorable properties for further development as an imaging agent for prostate cancer.
PMID: 16434567 [PubMed - indexed for MEDLINE]
 
Mass_69

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Sounds to me like it binds/blocks the AR, which is most likely not what you want (unless you have a prostate problem). :cool:
 
xtraflossy

xtraflossy

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Sounds to me like it binds/blocks the AR, which is most likely not what you want (unless you have a prostate problem). :cool:
I don't think it blocks the receptor, as the AR activation was needed to test.
"We investigated the use of nonsteroidal AR ligands for receptor-mediated imaging as a diagnostic tool for prostate cancer staging."

I MEAN, IT SAYS RIGHT THERE THAT WHAT THEY WERE USING WERE NON-STEROIDAL AR LIGANDS. tHAT WOULD MEAN IT ACTIVATES THE AR.
-right?
(damn caps lock)
 

same_old

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I don't think it blocks the receptor, as the AR activation was needed to test.
"We investigated the use of nonsteroidal AR ligands for receptor-mediated imaging as a diagnostic tool for prostate cancer staging."

I MEAN, IT SAYS RIGHT THERE THAT WHAT THEY WERE USING WERE NON-STEROIDAL AR LIGANDS. tHAT WOULD MEAN IT ACTIVATES THE AR.
-right?
(damn caps lock)
activates the AR???

dude, it binds to the AR. this is bad. we want our steroids (or natty test, for the anabolically resistant) to bind to the AR, not some ligand with no anabolism.

aldactone already does this.

a topical version would be great for MPB sufferers, though. really great in fact. IBE??? Carlito???
 
xtraflossy

xtraflossy

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Lol- I thought it may have been non-steroidal that activates the AR, Like a selective amdrogen receptor modulator (sARM).
Which was one of the things that is being looked at by supplemental companies and the pharm. Industry-
If not, then just ignore,.. I thought it may be usefull becasue it ca nhot the AR, bit remain unbound, and had a simular affinity to test.
 
Mass_69

Mass_69

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Even with a SARM, it may "activate" ARs in certain body parts, but "block them in others. Kinda like SERMs (at least Clomid & Nolva), they are anti-E in certain regions, but have an estrogenic (mild) effect in others.
 

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