MK-4541 kills prostate cancer, makes muscles stronger

Evil Spock

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https://www.ncbi.nlm.nih.gov/pubmed/24565564

Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.
Schmidt A1, Meissner RS2, Gentile MA3, Chisamore MJ3, Opas EE3, Scafonas A3, Cusick TE4, Gambone C3, Pennypacker B3, Hodor P5, Perkins JJ2, Bai C3, Ferraro D3, Bettoun DJ3, Wilkinson HA3, Alves SE3, Flores O3, Ray WJ6.
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Abstract
Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens.
 
https://www.ncbi.nlm.nih.gov/pubmed/24565564

Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.
Schmidt A1, Meissner RS2, Gentile MA3, Chisamore MJ3, Opas EE3, Scafonas A3, Cusick TE4, Gambone C3, Pennypacker B3, Hodor P5, Perkins JJ2, Bai C3, Ferraro D3, Bettoun DJ3, Wilkinson HA3, Alves SE3, Flores O3, Ray WJ6.
Author information

Abstract
Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens.

Interesting. I'll keep my eyes open for further info as this moves forward.
 
This is very interesting. Someone close to me was recently diagnosed. Thanks for sharing this info!
 
Nice find for sure, my father is 2 years past his diagnosis and total prostatectomy. Clean bill of health now. Wonder if anyone will start to carry this sarm?. @vancitybb if ya need someone to talk to about it shoot me a pm.
 
Nice find for sure, my father is 2 years past his diagnosis and total prostatectomy. Clean bill of health now. Wonder if anyone will start to carry this sarm?. @vancitybb if ya need someone to talk to about it shoot me a pm.

Really appreciate that bro. That's great news about your father.
 
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