Excellent YK-11 article by Mike Arnold

[Stewie]

I'd like a definitive answer on how much YK-11 inhibits other AAS being that it's a partial androgen receptor antagonist. All over online bro-science speculates YK-11 is a DHT derivative. I wonder if there are enough androgen receptors to run a gram of test with YK-11 and not have any inhibition of the test at that dose.
Stewie, are progesterone derivatives activated via the androgen receptor?
I assume all AAS are dependent on the androgen receptor?
The question is what is the maximum dose of AAS that's not wasted by over saturation of the androgen receptor?

How do we know it possesses antagonistic properties?

As for progestins and androgens they elicit their effects on few receptors-- glucocorticoid receptors and androgen receptors.

The rest of your questions. I dunno?

As for it being a DHT derivative or not... I could give two fucks less what anyone else says.


I trust Patrick Arnold and b_cornelius call on this... Everyone's else's so-called opinion is null and void.

I would not underestimate b_cornelius intelligence.

I trust actual chemists on this. Not a coach.

 

[micro2000]

How do we know it possesses antagonistic properties?
.

I haven't read the 2 papers on YK, but doesn't one show that it is partial antagonist at the AR?

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[Stewie]

I haven't read the 2 papers on YK, but doesn't one show that it is partial antagonist at the AR?

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You may be correct, although I've only seen it reported as a partial agonist.

 

[micro2000]

You may be correct, although I've only seen it reported as a partial agonist.

My bad, partial agonist. So effectively it would diminish the activity of another agonist. Not a true antagonist, though.

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[Stewie]

My bad, partial agonist. So effectively it would diminish the activity of another agonist. Not a true antagonist, though.

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Interesting.

I must say, I'm not following here. Although not structurally the same as an androgen would it not created a dimer, exerting either an additive or a synergistic effect?

I'm sure there's a simple explanation, just my heads not screwed on straight.

Thanks

 

[micro2000]

Interesting.

I must say, I'm not following here. Although not structurally the same as an androgen would it not created a dimer, exerting either an additive or a synergistic effect?

I'm sure there's a simple explanation, just my heads not screwed on straight.

Thanks

From memory of the abstract, YK reduced AR activation in the presence of DHT.

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[Stewie]

Here's my prebed thoughts.

Yk-11 was analyzed via in vitro through cell line cultures (C2C12 cells).

There's over a hundred androgen receptor interacting proteins involved with completed action upon the AR--- nuclear receptor coregulators, signal integrator/transducer, scaffold, adaptor, etc, ect, etc.

Only two or three proteins cell lines were used with Yk.

...In vivo would these actions be replicated?

Something to sleep on.

 

[micro2000]

Agree with your assessment. In-vivo and in-vitro rarely mimic each other. The problem is that we only have 2 in-vitro studies on this compound and people are already using it.

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[Stewie]

Agree with your assessment. In-vivo and in-vitro rarely mimic each other. The problem is that we only have 2 in-vitro studies on this compound and people are already using it.

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Phase III ProMuscle clinical trials

 

[micro2000]

Phase III ProMuscle clinical trials

I can imagine a company presenting the FDA a binder full of logs from the internet.

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[boxer cam]

Hopefully by page 100 of this thread we have the answers about YK-11. Definitely going to be very interesting to follow and a big thanks to the guys with the testicular fortitude to try it out.

 

[Stewie]

If we could find a private lab or a medical university that'll do a ligand competition binding assay for the androgen receptor, we would start to put an end to the confusion.

 

[nothuman]

Anyone using this have any updates?

 

[b_cornelius]

I'm back.

I see that we have boiled this down to the science vs common sense thing again. My point is that this whole thing is only science so far. We have recently seemed to have crossed a new line with these research chemicals, and that has been troubling me. A year ago, YK (along with a few other new offerings) was just a pipe dream in a chemist's mind, and there were no real tests done. The whole RC industry has sped up.

There are always risks involved, but before the chemicals offered had undergone more testing. Now with things such as YK, we didn't even know where to begin...It had only been tested in a few test tubes. We didn't really know what dose to take, we didn't know how it was metabolized... and despite the liver, we still don't know how it's toxicity plays out in other systems.

These market developments have been unconsciously bothering me, and we have so many people purveying and selling this crap. While I don't have a problem with the Op's (JJ's) attitude towards these things, I did take offense to Mike since he was responsible for the article. From there, I took an unreasonable attitude towards Mike.

While I don't feel sorry for the relative truths that I spit out, I do feel sorry that I undermined my neutrality in such a way that was unnecessary. I overplayed my hand and said a few things that you don't say in a logical conversation. Oh the fee fees.

I do feel sorry for the unreasonable attitude that I took towards Mike, and yet I hope he knows that I do hold him to a higher standard since he is out there publishing these articles.

From what I know, since I have been following YK since it's first publication, YK is indeed a rarer skeleton known as the pregnane , and it is a 19-nor at that. The pregnane has somewhat of a "natural" signification, compared to methyl, because at the 17th position because it is an ethyl. But it is in no way a Dihydro... so yes it may be a 19 nor, but definitely not a methyl. It has an ethyl group on the 17th position, and from there, there is a bunch of other $h!t attached and don't know the ramifications of it.

 

[Cinder]

So yk is done.

 

[Barny]

I stole this info from another board. Not sure about posting links to other boards, so I am not going to do it.


YK11 stimulates the creation of follistatin. When YK11 is in the presence of follistatin, it causes a large sudden production of myogenic differentiation factor (MyoD), myogenic factor 5 (Myf5) and myogenin. The three myogenic items are what causes the body to create new muscle cells. Testosterone and DHT compounds also do this, but without the creation or need for follistatin. Well, not quite correct, testosterone does induce the creation of follistatin, just not nearly at the same level as YK11. Normally, the body produces myostatin as a counter to mygenin (it competes for the same receptors and then encourages the body to destroy the newly created muscle cells), to help keep the body from just making more and more muscle (which is normally what we want). Follistatin aids in the reducing the effect of myostatin in a few ways, but that is outside the scope of what I am talking about. It is this follistatin that makes YK11 so powerful compared to testosterone or DHT compounds (and why testosterone is still a better choice for muscle creation than other AAS - it is a perfect item to use in synergy with other items).

The human body, being an insanely amazing thing, is not powerless against follistatin. As follistatin levels rise, it creates an anti-follistatin antibody. This anti-body helps restore the body back to its normal state so there is not run-away muscle creation (again, that would be a bad thing).

YK11 is only partially androgenic and it has the same effects on FKBP51 as DHT compounds do, in other words, it increases it quite a bit. This is only a problem if you currently have cancer, as FKBP51 is instrumental in cell survival and it will also greatly aid cancer cells in their survival. If you have cancer, do not take YK11...and also do not take any compound that turns into DHT in the body. Yeah, that is just about every good AAS out there. Remember, cancer is no joke, so if you have it, getting rid of it should be your number one priority...not gaining muscle. Don't be a loser about it and die just to look good at your funeral. For the vast majority of people without cancer, there is no problem with having an increased FKBP51 level. Increased FKBP51 levels does NOT cause cancer.

I have found no side effects at all for YK11 (other than the increase in FKBP51, which you also find in most AAS), but it is still a very new SARM so only time will tell. EDIT: YK11 apparently reduces the strength and elasticity of connecting tissues. It would be wise to use it in conjunction with something that increases the strength of connecting tissues, such as HGH.

There is also no suggested dosing by the medical community, again due to it being so new. As far as I can tell, it has yet to be used on a live creature by the medical community - it has only been used on cell cultures. At least they were human cell cultures. Welcome to the bleeding edge here folks! I have included a nice picture showing that follistatin and myostatin compete for the same receptors. Myostatin encourages muscle atrophy, follistatin encourages muscle creation (more or less correct for both).

YK11 also does not appear to cause the creation of Estrogen - it appears to do the same thing as Tamoxifen (though through a completely different method) but to a far lesser degree. YK11 cannot be used as a SERM replacement so please do not try.

What we need to keep an eye out for is nosebleeds. ACE31 was a myostatin inhibitor with great promise, made it into phase 2 human trials where they tested it on both people with muscular dystrophy and healthy people. It caused bad nosebleeds that stopped when the drug was no longer taken. It has been shelved until someone can figure out how to stop the bleeding. Since YK11 also appears to inhibit myostatin (though through completely different mechanisms), there is always the chance it will cause nosebleeds as well. They have no idea why ACE31 causes nosebleeds, but it did it with enough power and frequency to kill what looked like a huge money maker for the big pharma developing it. I doubt YK11 will cause nosebleeds, due to the way it works, but it is better to keep an eye out for it and it never happen than it to happen and you think it is caused by the change in seasons.

Sources:
https://www.jstage.jst.go.jp/article/bpb/36/9/36_b13-00231/_html
https://www.ncbi.nlm.nih.gov/pubmed/21372378

 

[Titan. gel]

I didn't see anything that much from it so I stopped selling it. I still have a bottle left purely for research.

 

[Titan. gel]

yk11 treatment of C2C12 cells, but not DHT induced the expression of follistatin , and the YK11-mediated myogenic differentiation was reversed by anti-Fst antibody.
These results suggest that the induction of Fst is important for the anabolic effect of YK11.

Quote from a study .


A novel steroid compound, (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11)

This was found to be a partial agonist of the androgen receptor (AR) in an androgen responsive element (ARE)-luciferase reporter assay. YK11 accelerates nuclear translocation of AR. Furthermore, YK11 does not induce amino/carboxyl-terminal (N/C) interaction and prevents 5-α-dihydrotestosterone (DHT)-mediated N/C interaction. Thus, YK11 activates AR without causing N/C interaction, which may in turn be responsible for the partially agonistic nature of YK11 observed in the ARE-luciferase reporter system. YK11 acts as a gene-selective agonist of AR in MDA-MB 453 cells. The effect of YK11 on gene expression relative to that of androgen agonist varies depending on the gene context. YK11 activated the reporter gene by inducing the translocation of the AR into the nuclear compartment, where its amino-terminal domain (NTD) functions as a constitutive activator of AR target genes. Our results suggest that YK11 might act as selective androgen receptor modulator

MDA-MB 453 CELLS are studied for their AR abilities.

The role of androgens and the androgen receptor (AR) in the development and progression of breast cancer is poorly understood. To further define a potential model for androgen action in breast cancer, MDA-MB-453 cells, which express AR in the absence of oestrogen receptors and progesterone receptors, were further characterised in terms of AR expression and androgen responsiveness. High level expression of AR was confirmed by northern blot analysis, radioligand binding and immunocytochemistry, and could not be accounted for by AR gene amplification. Three endogenous androgen-responsive genes (fatty acid synthetase, gross cystic disease fluid protein of 15 kDa and prolactin receptor) and a transfected reporter gene, containing an androgen-responsive element, were induced following androgen administration. A synthetic androgen, mibolerone, induced moderate (27% above control) stimulation of MDA-MB-453 cell proliferation, which was abrogated by the simultaneous administration of the synthetic androgen antagonist, anandron, demonstrating that the effect was AR-mediated. In summary, MDA-MB-453 cells express high levels of functional AR, and thus provide a valuable in vitro model for further studies on androgen regulation of gene expression, and perhaps cell proliferation in breast cancer.

The greatest amounts of MDA-MB-453 cells are found in breast tissues, I am speculating would YK11 help treat gyno, as its target AR is a triple negative?
This ties in with barnys post..

Maybe Stewie, or Cornelius could clear this up?

 

[Thebigone]

I didn't see much st 10mg per day except my heart rate elevated a lot so I stopped.

 

[micro2000]

yk11 treatment of C2C12 cells, but not DHT induced the expression of follistatin , and the YK11-mediated myogenic differentiation was reversed by anti-Fst antibody.
These results suggest that the induction of Fst is important for the anabolic effect of YK11.

Quote from a study .


A novel steroid compound, (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11)

This was found to be a partial agonist of the androgen receptor (AR) in an androgen responsive element (ARE)-luciferase reporter assay. YK11 accelerates nuclear translocation of AR. Furthermore, YK11 does not induce amino/carboxyl-terminal (N/C) interaction and prevents 5-α-dihydrotestosterone (DHT)-mediated N/C interaction. Thus, YK11 activates AR without causing N/C interaction, which may in turn be responsible for the partially agonistic nature of YK11 observed in the ARE-luciferase reporter system. YK11 acts as a gene-selective agonist of AR in MDA-MB 453 cells. The effect of YK11 on gene expression relative to that of androgen agonist varies depending on the gene context. YK11 activated the reporter gene by inducing the translocation of the AR into the nuclear compartment, where its amino-terminal domain (NTD) functions as a constitutive activator of AR target genes. Our results suggest that YK11 might act as selective androgen receptor modulator

MDA-MB 453 CELLS are studied for their AR abilities.

The role of androgens and the androgen receptor (AR) in the development and progression of breast cancer is poorly understood. To further define a potential model for androgen action in breast cancer, MDA-MB-453 cells, which express AR in the absence of oestrogen receptors and progesterone receptors, were further characterised in terms of AR expression and androgen responsiveness. High level expression of AR was confirmed by northern blot analysis, radioligand binding and immunocytochemistry, and could not be accounted for by AR gene amplification. Three endogenous androgen-responsive genes (fatty acid synthetase, gross cystic disease fluid protein of 15 kDa and prolactin receptor) and a transfected reporter gene, containing an androgen-responsive element, were induced following androgen administration. A synthetic androgen, mibolerone, induced moderate (27% above control) stimulation of MDA-MB-453 cell proliferation, which was abrogated by the simultaneous administration of the synthetic androgen antagonist, anandron, demonstrating that the effect was AR-mediated. In summary, MDA-MB-453 cells express high levels of functional AR, and thus provide a valuable in vitro model for further studies on androgen regulation of gene expression, and perhaps cell proliferation in breast cancer.

The greatest amounts of MDA-MB-453 cells are found in breast tissues, I am speculating would YK11 help treat gyno, as its target AR is a triple negative?
This ties in with barnys post..

Maybe Stewie, or Cornelius could clear this up?

I don't think one could extrapolate from MDA cells any real world effects on gyno. MDA cells are a line of triple negative cancer cells, meaning they lack estrogen, progesterone and HER2 receptors, which are all targets for chemotherapeutics. Gyno is benign tissue growth, whereas triple negative cells are fast growing metastatic cancer cells.

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