What do you say to this, dear researchers?
http://www.*************.com/forum/s...ad.php?p=54751
What do you say to this, dear researchers?
http://www.*************.com/forum/s...ad.php?p=54751
Arrg - Whats the website? Am I going to grow a 3rd arm?
hmmm, 3rd arm...
andarine is not the same as ostarine...
andarine = s1
ostarine =s4
The link doesn't work? Well, I will post it here:
S-4 Warning S-4 Warning is offline
Junior Member
Join Date: Dec 2009
Posts: 1
Default S-4 Warning
To all thinking of SARMs....
Be aware that S-4 is NOT Ostarine! This myth has been promoted by black market sellers of S-4. It is not true.
S-4 is Andarine (of GTx formerly under development w/ J&J).
(See: http://www.sciencedaily.com/releases...cience+News%29)
ANDARINE WAS STOPPED IN DEVELOPMENT GIVEN SERIOUS ADVERSE EFFECTS!
I'm not a muscle builder - I work in pharma. So I write ONLY as I've become VERY concerned by the VERY common error that is on this board and others that S-4 is Ostarine - even the structure of Ostarine on Google today is wrong! (It is S-4). And horrified to learn hear of folks taking or considering taking S-4, given its known serious adverse effects, which are FAR WORSE than other SARMs in development or even old anabolic steriods (even with all their known adverse effects).
Serious occular events were seen with S-4, due to a known metabolism problem. These problems are NOT limited to occular issues - just that occular issues are some of the first seen.
Ostarine is a very similar bicalutamide based structure to S-4. Results on occular effects have yet to be reported with Ostarine. In fact as of today (Dec 2009) there is still NO peer reviewed medical article on any Ostarine HUMAN DATA. Only a brief presentation at ENDO 2009 and two posters at prior meetings. And note that GTx and Merck (Ostarine partner) have yet to report the start of any new human study with Ostarine since the start of their partnership in Dec 2007.
BUT "Body of Science Man" is kinda right that not all SARMs work the same. They have different gene transcription effects (McDonnald et al, 2009). But by definition, ALL SARMs work as ligands to the ligand binding domain of the Androgen Receptor. If it doesn't bind to the AR, its not a SARM.
But statements like "S-4 is the best SARM by far" of that it is "available" ethically, are simply not true.
Also, BMS-564,929 (NOT the strongest SARM ever synthetized) was also discontinued in early human safety studies.
It is really confusing, because Wikipedia says S-1=Andarine, S-4=Ostarine.
However, this article states that S-4 is actually Andarine and Ostarine is a similar, but different stuff called MK-2866
http://pubs.acs.org/doi/abs/10.1021/jm900280m
S-1 has no commercial name.
Last edited by Steroidman99; 12-09-2009 at 07:09 PM.
And you are basing that on what - above article?
If you noticed, its not an article, rather its someone mentioning that xxx is not yyy and it has adverse effect and study was stopped. Everything that he mentioned is already known, including S1 being similar to S4 - so what study was stopped, on animal, on human, what is the major adverse effect?
This person could be 100 percent right that S4 is not Ostarine but post above adds zero value as it stand. So lets see what others dig up before making any concrete statement. Else we all would believe no one should be doing AAS since its so dangerous substance that kills thousand (or what mainstream will have us believe). cheers!
Funny all you have to do is type ostarine in pubmed and you get a bunch of studies?
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I copied the post from Body of Science forums. As you can see, the man claims that he is an expert in this field. However, he hasn't replied to my questions so far.
I myself am not aware of any study that would find S-4 toxic, and according to a recent review of SARMs (Zhang et al.: Recent advances in the development of selective androgen receptor modulators, 2009), "BMS-564929 has advanced into clinical trials for the treatment of age-related functional decline". I only know that LGD-2226 was discontinued because of toxicity.
I thought over ordering SARMs, but this info made things complicated. I will probably contact some experts, because I don't want to be a lab rat.
I thought the same and I normally wouldn't believe it. However, this review claims the opposite:
http://pubs.acs.org/doi/abs/10.1021/jm900280m
This is just some of the silliest crap I've heard. Ostarine is the compound name of a substance that has the chemical formula: (S)-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide, which is abbreviated colloquially as S-4. It has the CAS number "401900-40-1", which, when you look it up, will give you the patents and clinical trial results for Ostarine, along with the structural formula for S-4. GTx refers to Ostarine also as "MK-2866", a name which follows the terminology used by MercK (ah,ha, you get it) for new compounds made by Merck which you haven't decided a creative brand name for yet. S-4 = Ostarine = MK-2866 = compound with CAS #401900-40-1.
So, S-4 was synthesized. Merck calls is MK-2866 before the structure is known/before it's patented/before it's given a sexy drug name, Ostarine. When you register the compound, it gets the tag of CAS# 401900-40-1, a system which was invented so people all can know exactly what compound you're talking about. Any questions?
I am sorry that you couldn't read that article. Here is an excerpt:
http://pubs.acs.org/doi/abs/10.1021/jm900280m
"...The resulting compound known
in the literature as S-4 and in press releases as andarine (8,
S-3-(4-acetylaminophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-
trifluoromethylphenyl)propionamide) (discussed below) was
shown to possess SARM activity and allowed the pharmacodynamic
exploration of this novel class of drugs, as discussed
in section 2."
"Readers are cautioned to note
that the name Ostarine is often mistakenly linked to the chemical
structure of 8, which is also known as andarine. The chemical
structure of Ostarine has not been publicly disclosed. The
authors are unable to provide additional information."
Another recent article clearly distinguishes S-4 and Ostarine/MK-2866 as well
http://informahealthcare.com/doi/abs...43770902994397
"In 2003, Johnson & Johnson (J & J) and GTx initiated a Phase I trial of andarine for cancer cachexia. Merck and GTx are at present conducting a Phase II trial of Ostarineâ„¢ (MK-2866) for cancer cachexia."
"The lead compounds (S-1 (1), S-4 (2), C-6 (3), S-23(4) and 5 in Figure 1) bind to the AR with affinity in the low nanomolar range and demonstrate a high degree of tissue-selective pharmacological activities..."
"Recently, GTx disclosed that compound 5 [36] had advanced into clinical trials. The patent application described detailed data in an initial proof-of-concept Phase IIa clinical trial. It is not explicitly stated that compound 5 is Osterine (MK-2866)."
![]()
If this is what AR-R is selling as it's S-4
(S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide)
then that's the S-4 used in research studies
http://dmd.aspetjournals.org/content/34/10/1713.full
Compound S-4 (S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide) is a novel nonsteroidal androgen agonist that mimics many of the beneficial pharmacologic effects of testosterone with lesser effects on the prostate. S-4 demonstrated high androgen receptor binding affinity as well as anabolic specificity during in vivo pharmacologic studies in rats, identifying it as the first member of a new class of selective androgen receptor modulators. The purpose of these studies was to determine the pharmacokinetics and metabolism of S-4 in dogs. S-4 showed linear pharmacokinetics after both intravenous (i.v.) and oral (p.o.) administrations at pharmacologically relevant doses, with a mean clearance of 4.6 ml/min/kg and a mean half-life of about 200 min. It is interesting that dose-dependent oral bioavailability was seen. However, at pharmacologically relevant doses, the oral bioavailability of S-4 was 91%.
These in vivo findings corroborate our in vitro metabolism studies and suggest that S-4 may demonstrate suitable pharmacokinetics, oral bioavailability, and metabolism for use in humans.
Again - my only question is what is the correct dosage for humans to take.
I would certainly go off of your collected research you posted on CEM.
There is definite uncertainty of what is causing the occular issues. Wether it is mehtanol or the product(SARM) itself, if you want to avoid the issue, you don't want to follow the path everyone else has and use high doses.
So if i am to understand this correctly then the current S$ most people are taking is not the same drug the original poster is talking about?
The review cited above published by GTx specifically states andarine is S-4, and ostarine's structure is undisclosed. Andarine (S-4) was an early generation SARM stopped in development due to metabolic issues. Don't be fooled by the unreliable internet sources such as wikipedia. GTx is obviously aware of such arrogance and trying set things straight
If you look at the lab report on AR-R it says that its Ostarine
So then we get back to the dosage question
http://www.internationalbiotrust.com...8_Dec_06_2.pdf
Ostarine also exhibited tissue selectivity with beneficial effects on lean body mass and performance and with no apparent change in measurements for serum PSA (prostate), sebum production (skin and hair), or serum L (pituitary) compared to placebo.
http://www.istockanalyst.com/article...icleid/3294440
GTx, Inc. (Nasdaq: GTXI) today announced results of a Phase II clinical trial evaluating Ostarineâ„¢ (MK-2866), an investigational selective androgen receptor modulator (SARM), in patients with cancer induced muscle loss, also known as cancer cachexia. In the study, Ostarine treatment led to statistically significant increase in lean body mass (LBM) and improvement in muscle performance measured by stair climb in patients with cancer cachexia compared to baseline in both the Ostarine 1 mg and 3 mg treatment cohorts. These study results were the subject today of an oral podium presentation at the 2009 Annual Meeting of the Endocrine Society in Washington.
In the study, Ostarine met the primary endpoint of LBM, measured by a dual energy X-ray absorptiometry (DEXA) scan, by demonstrating statistically significant increases in LBM compared to baseline in both the Ostarine 1 mg and 3 mg treatment cohorts. Specifically, the change from baseline in LBM for the placebo, 1 mg and 3 mg treatment groups was 0.1 kg (p=0.874 compared to baseline), 1.5 kg (p=0.001) and 1.3 kg (p=0.045), respectively, at the end of the 16-week trial.
At a dose of 1mg per DAY - the gain in LBM was 3.3 pounds
Ostarine IS S-4
http://www.ganolix-pharm.com/product/164.html
GTx Announces Ostarine Improved Insulin Resistance among Elderly,Patients in a Recently Completed Phase II Clinical Trial
http://www.bio-medicine.org/medicine...l-Trial-973-1/
The problem is the dosage
Go for 50 mg and see if u like it... Its hard to find out whats the dose on something this new.... Its been tried at 200+ 100+ and they give side effects... If u want to avoid the visión problem take less (50mg) or don't take it( not being a jerk)
The recent review "Zhang et al.: Recent advances in the development of selective androgen receptor modulators (2009)"
http://informahealthcare.com/doi/abs...43770902994397
actually contains the chemical structure of Ostarine ("5"). I overlooked it before.
It differs from S-4 by NHAcetyl and N2O groups instead of CN. (Chemistry is not my field, so correct me, if I am wrong.)
The review tells nothing about any toxicity of S-4.
"In castrated rats, both S-1 and S-4 prevented castration-induced bone and muscle weight loss: only partial agonism was observed in the prostate (S-4, ED50 = 2 mg/(kg day)) whereas full agonist activity was seen in the levator ani muscle (S-4, ED50 = 0.6 mg/(kg day)). Prolonged treatment (8 weeks) with S-4 also restored tissue weight loss 3 months after castration. At the 3 mg/(kg day) dose level, S-4 restored the prostate weight to in 20% of intact level and fully restored the levator ani muscle weight to control level. In addition to these tissues, S-4 demonstrated strong anabolic effects in restoring skeletal muscle (i.e., soleus muscle) strength, total body bone mineral density and lean mass.
In intact male rats, S-1 and S-4 functioned as antagonists in the prostate without abolishing the anabolic effects of androgens in the levator ani muscle or increasing gonadotropin release and plasma T concentrations, suggesting that SARMs with low intrinsic activity in the prostate might serve as an alternative therapy for BPH or even prostate cancer. Both S-1 and S-4 are orally bioavailable with in vivo half-lifes of about 4 h in rats [38,39]. Metabolism studies have shown that, similar to hydroxyflutamide and nilutamide, amide bond hydrolysis and nitro reduction are the major metabolic pathways observed in vivo [40]; these derivatives are eliminated exclusively through hepatic pathways and also showed species-dependent metabolism [41]."
S-4 is to be in "Phase I for cancer cachexia", while MK-2866 is in "Phase II for cancer cachexia".
"Recently, GTx disclosed that compound 5 [36] had advanced into clinical trials. The patent application described detailed data in an initial proof-of-concept Phase IIa clinical trial. It is not explicitly stated that compound 5 is
Osterine (MK-2866). The trial was a double-blind, randomized, placebo-controlled trial in 60 elderly men and
60 postmenopausal women. Without a prescribed diet
or exercise regimen, all subjects treated with 5 had a dose-dependent increase in total lean body mass, with the 3 mg/day cohort achieving an increase of 1.3 kg compared to baseline and 1.4 kg compared to placebo after 3 months of treatment. Treatment with 5 also resulted in a dose-dependent improvement in functional performance measured by a stair climb test, with the 3 mg/day cohort achieving clinically significant improvement in speed and power. Interestingly, subjects treated with 3 mg/day of 5 experienced on average an 11% decline in fasting blood glucose, a 17% reduction in insulin levels and a 27% reduction in insulin resistance (homeostasis model assessment) as compared to baseline, suggesting that SARMs might have therapeutic potential in diabetics or people at risk for diabetes. It was also noted that treatment with compound 5 also resulted in a dose-dependent decrease in low-density lipoprotein and high-density lipoprotein cholesterol levels, with the average low-density lipoprotein:high-density lipoprotein ratio for subjects treated with all doses of 5 remaining in the low cardiovascular risk category."
The Ostarine on Wikipedia thus really seems to be true Ostarine:
http://en.wikipedia.org/wiki/Ostarine
However, it actually lists results of studies done on S-4 (Andarine)...
Frankly, I don't know, who I am to believe.
Last edited by Steroidman99; 03-22-2011 at 12:19 AM.
Update:
http://www.medpagetoday.com/Endocrin...Steroids/17107
"S-4 is a nonsteroidal, arylpropionamide compound that activates certain androgen receptors, while having no effects or acting as an antagonist at others. GTx conducted a Phase I trial of S-4 about five years ago, but later dropped the compound in favor of a second-generation agent with the trade name Ostarine, which has completed Phase II trials in cancer cachexia and chronic sarcopenia."
"...This product with considerable anabolic properties is readily available without sufficient research on its undesirable effects; this is especially significant where uncontrolled dosing is applied and drug impurities with unknown effects are present in considerable amounts as observed in the studied material," Thevis said in a statement."
Wow, yeah. I'm just as confused too now. I checked Scifinder again, a massive chemical database system for CAS:401900-40-1. It gives the structure as listed on Wikipedia and the many names of the compound:
C19 H18 F3 N3 O6
Propanamide, 3-[4-(acetylamino)phenoxy]-2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-, (2S)-
N-[4-Nitro-3-(trifluoromethyl)phenyl]-(2S)-3-[4-(acetylamino)phenoxy]-2-hydroxy-2-methylpropanamide; Ostarine; S 4
But now if you look at the wikipedia page of Ostarine and look at the patent posted, it'll take you to a page with the synthesis of a compound named Gtx-007...which matches with andarine...Gtx-024 is supposed to correspond to Ostarine.
So... I'm not sure what to know or think. There's an error somewhere here, but it's at an academic level...
Ok, I've done some digging here and come to the following conclusions:
- S-4 is Andarine
- Andarine was not stopped due to adverse effects, Gtx simply thought that Ostarine had better commercial potential because of better binding affinity, had limited funding, and decided to invest in Ostarine development first.
- Ostarine had been misquoted as being S-4 in a number of texts, including academic ones.
- I think that the structure of Ostarine is as shown above, with a nitrile group. Chemical name (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide.
- Perhaps CAS # 841205-49-0. Described in Patent 2007161608 A1 20070712?
did you mean methanol? Are you serious? Why would methanol be found in s-4? I know that methanol can cause permanent blindness and blurred vision, these effects are from the byproducts it converts to after absorbtion, and a VERY small amount is all it would take to make someone blind, less than 10ml orally. With a statement like this, I am afraid to put 1mg of s-4 in my body. Someone clarify what this guy is saying about "mehtanol" please
Real Acetamidoxolutamide only dilutes in Peg300 or Ethyl alcohol.
C
Yup, alright, I'm quite confident of this now. I contacted the American Chemical Society about this, as their database listed S-4 as being Ostarine. They just replied:
"I am happy to report that the CAS record of interest has been corrected.
For your convenience, please find the attachment of the CAS record containing the corrected chemical name.
Thank you for informing us of the error. Please accept our apology for any and all inconvenience."
They now list S-4 as Andarine.
If you look at the patent here: http://www.freepatentsonline.com/20070161608.pdf
Page 87 shows a compound called "N-4" which matches with the structure of Ostarine posted earlier, and at the bottom of the first column, refers to this structure as "formula III". The next column describes how this formula III increased muscle mass and decreased fat mass in seniors at 3mg/day. I'm very willing to say that this structure is MK-2866, Ostarine, etc. While I think S-4,Andarine is anabolic and dandy, once Ostarine hits the market, that's when people are going to start seeing the real power of SARMs.
Well, thank you for the final illumination. Hopefully Ostarine "hits the market" soon.![]()
So how far did testing of Andarine go?
Did it get to human trials? I am not at all clued up on this.
Its a bit unnerving that there was such a widespread mistake, but is it true to say a lot of the research papers just talk about "s4"?
whoever is up to this is up to no good![]()
S1, S4, Andarine, or Astarine - as far as I know, S4 that we been using were around since 2006-7 when one person began supplying them. So far, side effect, short term wise, been predictable (every single rats). We do not know about long term and I doubt that the other version that OP mention knows either since its new.
S1 or S4 (Andarine or Astarine) both have qualities that we want - whether efficacy of one is better than another - we could only go by what was written. Still, even at lower efficacy, the version that we are experimenting seems to work.
If you are not comfortable, don't take it. Simple as that. People do worse than this (and are dying everyday from it), so you do what you are comfortable with.
So what is the point of this post - its good that someone wants to set the record straight. Other than that, nothing.
???
Sorry, I was just asking. Seems a mistake was made in naming by quite a few people.
I have been giving it ("s4") to my lab rat for the last 3 weeks and he is fine. He is an older lab rat, and I think it may be particularly benificial to older specimens.
I am not interested in who sells it or anything else. ???
I had the vision problems, and an extreme allergic reaction to s4. after about 4 or 5 days i started to get the hives and the boils and the vision problems. although the stuff does work as claimed, at least on me
Thats really interesting. I had a same allergic reaction - hives and bumps. My ear looked like I was boxing night before - severe cauliflower ear.
I didn't mentioned this before as I thought I had a food allergy at the time and was coincident that it happened at the end of my cycle. In the end, I had to get cortison injection from my doc. Guess I won't be doing S4 again.
wow, i had read about the possible vision problems but with several experiencing serious allergic reactions such as this it definitely makes you reconsider using S-4 a bit more. think im gonna hold off on trying something this new, as great as it seems it can be.
thanks everyone for posting on this, some very insightful stuff.
Poundcake - you got pm.
I don't know how severe of allergic reaction it was for poundcake but for me, I had to go to emergence care as my whole face and ear blew up. If you could imagine an elephant boy, I wasn't far off.
Luckily it didn't affect my breathing passage and after initial cortison shot, it went down quickly. Overall, it took 2 weeks to fully subside and all the skin to peel off. I've must used about a jar worth of vaseline as skin was super dry and itchy.
I'm still trying to nail down what actually caused it at this point. I've cut out pretty much everything I was eating and slowly re-introducing one at a time to find the culprit. Poundcake running into same thing leads me to believe S4 was the culprit but not 100% sure yet.
Man, I really want to run this stuff and put it to the test, but seeing stuff like this scares the hell out of me. If there's anyone else experiencing other sides besides the vision issues, please let it be known.
I didn't mean to scare ya bro!
There's only 2 of us that is known at this point, so its small percentage. Anyone doing this - just make sure you have extra strength Benedryl on hand.
Good thing is - all that peeling made my skin feel smooth. Beats the laser treatment - hah!
Last edited by endus; 12-29-2009 at 10:45 AM.
Actually MS, you dont. You get 2, none of which label it S-4.
So what exactly is S-4? If its not Ostarine?
Below is a study on Ostarine confirming its positive effects on LBM:
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 9119
© 2007 American Society of Clinical Oncology
Abstract
Ostarine increases lean body mass and improves physical performance in healthy elderly subjects: Implications for cancer cachexia patients
W. Evans, M. R. Smith, J. E. Morley, K. G. Barnette, D. Rodriguez, M. S. Steiner and J. T. Dalton
Donald W. Reynolds Center on Aging, Little Rock, AR; Massachusetts General Hospital, Boston, MA; Saint Louis University and VAMC, St. Louis, MO; GTx, Inc., Memphis, TN
9119
Background: Cancer cachexia results in selective loss of skeletal muscle resulting in weakness, reduced physical activity and a lower quality of life. Cancer cachexia also diminishes response to chemotherapy and survival. Anabolic steroids appear to increase weight and muscle mass in cancer patients, but have the potential for masculinization in women and prostate stimulation in men. A new class of non-steroidal selective androgen receptor modulators (SARMs) is being developed for use in cancer cachexia. SARMs are designed to have predominately anabolic activity in muscle and bone with minimal androgenic effects in most other tissues. We conducted a randomized phase II proof of concept study of ostarine, the first-in-class SARM, in healthy postmenopausal women and elderly men prior to intitiating a phase II study in cancer patients. Methods: Sixty elderly men (mean age 66 years) and 60 postmenopausal women (mean age 63 years) were randomly assigned to ostarine 0.1, 0.3, 1 mg, 3 mg or placebo for three months. The primary end point was change from baseline to three months in total lean body mass (LBM) measured by dual energy x-ray absorptiometry (DXA). The key secondary end point was a stair climb functional performance test that measured speed and power exerted. Evaluations included laboratory safety assessments and additional assessments of androgenic activity including PSA, sebum production and luteinizing hormone. Results: Ostarine treatment resulted in a dose dependent increase in total LBM, with an increase of 1.4 kg compared to placebo (p<0.001) at the 3 mg dose. Increased LBM translated to an improvement in the stair climb test in both speed (+15.5% ± 12.9 faster time, p=0.006) and power (+25.5% ± 20.3 watts, p=0.005). There were no serious adverse events reported. There were no significant changes in PSA, sebum production or luteinizing hormone. Conclusions: Ostarine improves LBM and physical performance in healthy older men and women. Ostarine had no unwanted androgenic side effects. A phase II study is planned to evaluate the safety and efficacy of ostarine in patients with cancer cachexia.
No significant financial relationships to disclose.
Abstract presentation from the 2007 ASCO Annual Meeting
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