Ostarine - SARM in Phase III Trials

Pharma / TRT
1

Hey,

Just wanted to get the word out that this new drug is currently beginning phase III trials, and a VERY reliable source said it could hit the market as soon as late 2010.

Ostarine is a non-steroidal selective androgen receptor modulator. The drug will be marketed at the elderly population, both men and women. Delaying andropause through drug therapy without acceptable side effects has been a challenge, but the clinical trials for this drug seem very promising.

So far it has shown to increase muscle mass in men and women, increase bone density in women, slow the growth of prostates in men and reduce the occurrence of breast cancer in women.

Kinda sounds like a miracle drug, huh? Even better is that the worst reported side effects so far have been nausea and diarrhea.

I know its sounds like I work for the company but I tried to write this in a way as to not tip off my identity. Let’s just say that I was taught by the head medicinal chemist responsible for compounding this molecule.

Just wanted to let everyone know to keep an eye out. The side effects of classic steroids could become a thing of the past if more SARMs are developed.

Here is the link companies website regarding Ostarine.

Forgot the link*

2

[quote]phiphika1453 wrote:

I know its sounds like I work for the company but I tried to write this in a way as to not tip off my identity. Let’s just say that I was taught by the head medicinal chemist responsible for compounding this molecule.

[/quote]

didnt that just completely tip off your indentity?

3

Probably not since he has probably taught 7-8000 medical/pharmacy/graduate students in his life time.

4

[quote]phiphika1453 wrote:
So far it has shown to increase muscle mass in men and women, increase bone density in women, slow the growth of prostates in men and reduce the occurrence of breast cancer in women.[/quote]

DHT will do all these too (seriously.) So can other synthetic anabolic steroids. They show tissue selectivity to. In fact they were developed on precisely that basis.

Now it may be the case that there is something to these drugs above and beyond existing anabolic steroids besides just being able to say “We don’t have a steroid ring structure, therefore we are not a steroid! Steroids are bad, you know!” Or some argument like that.

But if there is, the limited number of literature articles I’ve read on it never gave it. Nor does the website of this company. I just took “SARM” as being wanting to use a buzzword.

However, it could be that there is something that I missed.

Since you were taught by the head guy, hopefully you can elucidate.

5

[quote]Bill Roberts wrote:
phiphika1453 wrote:
So far it has shown to increase muscle mass in men and women, increase bone density in women, slow the growth of prostates in men and reduce the occurrence of breast cancer in women.

DHT will do all these too (seriously.) So can other synthetic anabolic steroids. They show tissue selectivity to. In fact they were developed on precisely that basis.

Now it may be the case that there is something to these drugs above and beyond existing anabolic steroids besides just being able to say “We don’t have a steroid ring structure, therefore we are not a steroid! Steroids are bad, you know!” Or some argument like that.

But if there is, the limited number of literature articles I’ve read on it never gave it. Nor does the website of this company. I just took “SARM” as being wanting to use a buzzword.

However, it could be that there is something that I missed.

Since you were taught by the head guy, hopefully you can elucidate.[/quote]

You are correct, anything that will bind the androgen receptor will stimulate the same gene expression. After all, its the androgen receptor protein itself that actually stimulates the gene expression required for increased muscle mass. Molecules with steroidal structures will bind the androgen receptor, but they also have many unwanted and dangerous side effects.

The #1 reason for developing this drug was to eliminate the side effects of steroids while still being able to bind the androgen receptor. Once the androgen receptor is bound, assuming binding affinities are similar, the receptor will just do its job. I have not seen any papers on the binding properties of Ostarine, but I would assume they are very similar to steroids since there are only so many amino acid residues capable of being bound in the androgen receptor.

So, like you said yes DHT will do all these things, but its the pros vs cons of side effects that will attract many physicians to this drug.

6

Also, I’m not sure who wrote the wikipedia article on SARMs but they did a good job of explaing what they are.

Didn’t even know this wiki article existed, lol. It’s about ostarine itself.

7

I really don’t know a lot about this, so this question may sound stupid, but if SARM’s work as advertised, does it appear that they would provide many of the benefits of a DHT derived steroid while avoiding the side effects of testicular atrophy, decrease in seminal production, and suppression (is that the right word?) of LH and FSH?

I am more of an ‘experience’ guy than a ‘science’ guy, so if I’m way off base just let me know.

8

[quote]Cortes wrote:
I really don’t know a lot about this, so this question may sound stupid, but if SARM’s work as advertised, does it appear that they would provide many of the benefits of a DHT derived steroid while avoiding the side effects of testicular atrophy, decrease in seminal production, and suppression (is that the right word?) of LH and FSH?

I am more of an ‘experience’ guy than a ‘science’ guy, so if I’m way off base just let me know.[/quote]

In a short answer, yes.

None of those side effects have been seen with the therapeutic doses SARMs as of yet. That’s why these drugs have made it to phase III trials. They still give the wanted results of increased muscle mass, bone density etc., but they have eliminated the classical side effects.

Remember anything can be toxic or show side effects with high enough doses, so don’t get carried away thinking this drug is a wonder pill. I am anxious to see actual results for my own eyes.

9

[quote]phiphika1453 wrote:
Bill Roberts wrote:
phiphika1453 wrote:
So far it has shown to increase muscle mass in men and women, increase bone density in women, slow the growth of prostates in men and reduce the occurrence of breast cancer in women.

DHT will do all these too (seriously.) So can other synthetic anabolic steroids. They show tissue selectivity to. In fact they were developed on precisely that basis.

You are correct, anything that will bind the androgen receptor will stimulate the same gene expression. After all, its the androgen receptor protein itself that actually stimulates the gene expression required for increased muscle mass. Molecules with steroidal structures will bind the androgen receptor, but they also have many unwanted and dangerous side effects.

The #1 reason for developing this drug was to eliminate the side effects of steroids while still being able to bind the androgen receptor. Once the androgen receptor is bound, assuming binding affinities are similar, the receptor will just do its job. I have not seen any papers on the binding properties of Ostarine, but I would assume they are very similar to steroids since there are only so many amino acid residues capable of being bound in the androgen receptor.

So, like you said yes DHT will do all these things, but its the pros vs cons of side effects that will attract many physicians to this drug.

[/quote]

But I can point you to a trial with DHT not showing adverse side effects either. Including not only no adverse side effects on the prostate, but improving BPH.

Many times the existing anabolic steroids at correctly chosen doses can show therapeutic benefits without side effects.

I am not saying it doesn’t exist, but as yet I have not seen the evidence-based reason that anything different is going on here at all. Nor a scientific reason why it would even be expected to be different.

Now in the case of the SERMs, it’s not just buzzword talk. The estrogen receptor actually is selectively modulated: it responds differently according to what is binding it.

If they had shown this true for the androgen receptor then it would not be just a buzzword. But I hadn’t seen that they or anyone had. So far as I know you are correct that any ligand that activates the AR yields the same gene expression. If that is in fact correct then the “selective modulator” phrase is just finding a buzzword and is misusing words. It might be smart marketing – in fact it undoubtedly is – but that there is any practical signifance to the ligand not happening to have a steroid ring structure, perhaps so but I have not any demonstration of it or even logical possible explanation. It would be interesting if there was one, though.

10

[quote]Bill Roberts wrote:
phiphika1453 wrote:
Bill Roberts wrote:
phiphika1453 wrote:
So far it has shown to increase muscle mass in men and women, increase bone density in women, slow the growth of prostates in men and reduce the occurrence of breast cancer in women.

DHT will do all these too (seriously.) So can other synthetic anabolic steroids. They show tissue selectivity to. In fact they were developed on precisely that basis.

You are correct, anything that will bind the androgen receptor will stimulate the same gene expression. After all, its the androgen receptor protein itself that actually stimulates the gene expression required for increased muscle mass. Molecules with steroidal structures will bind the androgen receptor, but they also have many unwanted and dangerous side effects.

The #1 reason for developing this drug was to eliminate the side effects of steroids while still being able to bind the androgen receptor. Once the androgen receptor is bound, assuming binding affinities are similar, the receptor will just do its job. I have not seen any papers on the binding properties of Ostarine, but I would assume they are very similar to steroids since there are only so many amino acid residues capable of being bound in the androgen receptor.

So, like you said yes DHT will do all these things, but its the pros vs cons of side effects that will attract many physicians to this drug.

But I can point you to a trial with DHT not showing adverse side effects either. Including not only no adverse side effects on the prostate, but improving BPH.

Many times the existing anabolic steroids at correctly chosen doses can show therapeutic benefits without side effects.

I am not saying it doesn’t exist, but as yet I have not seen the evidence-based reason that anything different is going on here at all. Nor a scientific reason why it would even be expected to be different.

Now in the case of the SERMs, it’s not just buzzword talk. The estrogen receptor actually is selectively modulated: it responds differently according to what is binding it.

If they had shown this true for the androgen receptor then it would not be just a buzzword. But I hadn’t seen that they or anyone had. So far as I know you are correct that any ligand that activates the AR yields the same gene expression. If that is in fact correct then the “selective modulator” phrase is just finding a buzzword and is misusing words. It might be smart marketing – in fact it undoubtedly is – but that there is any practical signifance to the ligand not happening to have a steroid ring structure, perhaps so but I have not any demonstration of it or even logical possible explanation. It would be interesting if there was one, though.
[/quote]

I think I understand what you are trying to say. The SERMs elict different responses b/c they have been developed enough to where they are highly tissue specific. Therefore they only act on estrogen receptors in the tissue desired therefore they will only cause the effects that activating estrogen receptors in that tissue can cause.

In other words, since the SERMs are so selective now, they won’t activate all estrogen receptors in the body. So its not the actual drug that is the difference b/w SERMs and SARMs; its where the estrogen receptor is located combined with the drug being designed to only concentrate in certain tissues.

At this point SARMs aren’t as selective for certain tissues as SERMs, so their effects are seen anywhere androgen receptors are found as long as the drug can access those receptors. Eventually, I think SARMs will be just as specific as SERMs. So this will give you the “specific” effect you are currently seeing in the SERMs

11

No, actually there is more to that. A given estrogen receptor responds differently according to what binds it. There are also tissue-specific differences in this so the same compound can be an estrogen agonist in some tissues, e.g. bone, while an antagonist in others, e.g. breast and uterine.

So the SERMs are not simply agonists or antagonists: they are modulators.

But the "SARM"s so far as I know are only agonists and don’t activate the androgen receptor any differently than anabolic steroids do.

If that is correct – and I’m open to it not being, it’s just that I have not seen anything showing it is not – then “SARM” is just a buzzword it seems to me.

12

[quote]Bill Roberts wrote:
No, actually there is more to that. A given estrogen receptor responds differently according to what binds it. There are also tissue-specific differences in this so the same compound can be an estrogen agonist in some tissues, e.g. bone, while an antagonist in others, e.g. breast and uterine.

So the SERMs are not simply agonists or antagonists: they are modulators.

But the "SARM"s so far as I know are only agonists and don’t activate the androgen receptor any differently than anabolic steroids do.

If that is correct – and I’m open to it not being, it’s just that I have not seen anything showing it is not – then “SARM” is just a buzzword it seems to me.[/quote]

Thanks for the breif explanation. I haven’t studied SERMs at all yet, so I had to do a little reading.

From the stuff I have read the different responses of SERMs are possible b/c the estrogen receptors themselves can elicit different responses based soley on which tissue they are located. So, like you said the same SERM is can upregulate in one tissue and down regulate in the other.

Can SARMs do this? I don’t know, but I would assume it all depends if the androgen recpetor can have the same dual functionality as the estrogen receptor. If this dual functionality exists then it seems obvious SARMs can be true modulators.

13

One other thought.

They may be calling these selective for the simple fact of lower side effects. If that is indeed true then they are “more” selective than current products for the androgen receptor; which would mean they don’t activate other, unwanted mechanisms.

Whatever their reason for using the term, you are 100% correct in saying its excellent marketing.

14

[quote]phiphika1453 wrote:
From the stuff I have read the different responses of SERMs are possible b/c the estrogen receptors themselves can elicit different responses based soley on which tissue they are located. So, like you said the same SERM is can upregulate in one tissue and down regulate in the other.[/quote]

No. As I said the estrogen receptor is activated differently according to what is binding it. This is true for both ER-alpha and beta. I wrote a review paper on this some years back, for graduate school not publication: maybe I can find it for you (but it may not be on this computer and if not then it is not practical to find. It certainly isn’t on this computer as any directly-existing file but may be buried within something else as part of some kind of backup. Just don’t know at the moment.)

I know of no evidence that this is the case for the androgen receptor. (Btw when I use that construction that is not a smarmy way of saying “I know there is no evidence,” it is just a literal statement that I don’t know it – but it’s not that I know all the evidence in this field.)

And as I said with the SERMs, a given one can be an agonist in one tissue and an antagonist in another. (Which differs from your statement regarding regulation of the number of receptors.) If anyone has evidence that this is ever the case for the "SARM"s that would be very interesting. I haven’t seen it. So far as I know they are nothing but agonists.

As for the claims of no side effects: There are plenty of women that have been prescribed, for example, Anadrol at 50 mg/day with no side effects either, except on the liver, which has nothing to do with androgenic properties but rather the alkylation. And plenty with oral Primobolan at that dose and no side effects at all. And back when the synthetics were first developed they were fairly commonly given to women and children. It is EASY to set up a study in such a way that a measurable therapeutic outcome will occur but quite likely no adverse side effects will be reportable. I am not at all sure anything has been demonstrated with regard to the "SARM"s in this regard as has not already similarly been demonstrated in many studies with plain ol’ anabolic/androgenic steroids.

(Note, please no one interpret the above as meaning those doses carry no risk for women. They do. The point is that medically they were considered non-problematic, based on clinical studies and even in practice. Primobolan has never been available in the US, but Anadrol was used for quite some time. For that matter Winstrol is probably still used for women but at quite low dose, but still enough to claim therapeutic benefit. So that it can be claimed that the "SARM"s have “no side effects” does not prove, merely from the claim, that actually anything different must be going on.)

15

Just wanted to say this is a pretty fascinating discussion IMO.

Carry on.

16

By the way, all this said: Even if (if) their using this term has no pharmacological validity at all and if these are utterly no different than anabolic steroids showing high anabolic/androgenic ratio except for not happening to be built on a steroid structure, results in getting the products on the market and prescribed to the elderly to enhance their quality of life, which I’ve long believed should have been far more common with anabolic steroids, that is a great thing.

Maybe they won’t do a thing different or better than, say, oral Primobolan.

But oral Primobolan is not being prescribed to the elderly to help them retain ability to function in daily life – to remain able to carry their own groceries in, to remain able to walk up the stairs, etc – and to help retain their bone mass, and it never will be. The reasons not are stupid, but not overcomeable. So if using a different catchphrase, and being able to tout “These aren’t steroids!” gets the job done, very good.

17

[quote]Bill Roberts wrote:
phiphika1453 wrote:
Bill Roberts wrote:
phiphika1453 wrote:

But I can point you to a trial with DHT not showing adverse side effects either. Including not only no adverse side effects on the prostate, but improving BPH.

[/quote]

Please point me; I could not find this.

18

deLignieres B. Ann Med (1993) 25 235

I did mis-write above: I should have written “study” not “trial.”

19

[quote]Bill Roberts wrote:
By the way, all this said: Even if (if) their using this term has no pharmacological validity at all and if these are utterly no different than anabolic steroids showing high anabolic/androgenic ratio except for not happening to be built on a steroid structure, results in getting the products on the market and prescribed to the elderly to enhance their quality of life, which I’ve long believed should have been far more common with anabolic steroids, that is a great thing.

Maybe they won’t do a thing different or better than, say, oral Primobolan.

But oral Primobolan is not being prescribed to the elderly to help them retain ability to function in daily life – to remain able to carry their own groceries in, to remain able to walk up the stairs, etc – and to help retain their bone mass, and it never will be. The reasons not are stupid, but not overcomeable. So if using a different catchphrase, and being able to tout “These aren’t steroids!” gets the job done, very good.[/quote]

Yes. Yes. Yes!!!

20

[quote]Bill Roberts wrote:
deLignieres B. Ann Med (1993) 25 235

I did mis-write above: I should have written “study” not “trial.”
[/quote]

From the abstract (I cannot download the full article so the methodology is unclear)
“A 1.8 years survey of 37 men aged 55-70 years treated with daily percutaneous DHT treatment suggested that high plasma levels of DHT (> 8.5 nmol/l) effectively induced clinical benefits while slightly but significantly reducing prostate size. Early stages of prostate hypertrophy require synergic stimulation by both DHT and oestradiol, and suppressing oestradiol instead of DHT seems easier and better adapted to the specific situation of aged hypogonadic men”

I had to ask, Friend Bill, since this one trial in 37 men, now over 16 years old, is contrary to a very large pile of clinical trials about treating or preventing BPH with reductase antagonists.

I speculate: perhaps the trial is not large enough, or long enough, to detect to detect real changes in prostate volumes (Or did this trial even measure volume, or only symptoms?)
However much I want the last sentence to be true, it remains unproven, since aromatase inhibition does not consistently reduce BPH, perhaps because of a rise in T and DHT that occurs in intact men treated with AIs.

Thanks for the reference.