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18 juli 2020, 18:46 | #11 |
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Geregistreerd: 12 augustus 2016
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Sommige mensen hebben ook PFS symptomen van minoxidil, interessante studie met mogelijke reden.
Minoxidil may suppress androgen receptor-related functions Abstract Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a Kd value of 2.6 ?M. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases. Interestingly, our structural studies demonstrated that minoxidil is chelated at a novel, previously unreported groove in the AR… Moreover, the groove is also located opposite to and at a distance from AF-2 and BF-3 sites…accordingly, it may represent a new candidate site for the interaction of AR coregulators. In our model, variations in this region resulted in steric clashes or changes in secondary structure. By occupying this grove, minoxidil may hinder the physical association of interacting proteins, thereby disrupting downstream regulation of AR transactivation. Taken together with mutagenesis data, our structural findings suggest that this groove may be important for binding of AR-interacting proteins during transactivation. |
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bijwerkingen finasteride, bijwerkingen minoxidil |
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