None of these four is a SARM. What MK-677, Cardarine, SR-9009 and SR-9011 actually do, which ones have human trials, and why two were abandoned on safety grounds.
25 min read
MK-677, GW-501516, SR-9009 and SR-9011 are sold together as SARMs. Not one of them is a SARM, and not one of them binds the androgen receptor. They are four unrelated molecules acting on four different receptor systems, and the only thing they share is that none has ever been approved for human use in any country, while two were abandoned by the companies developing them on safety grounds. This is the second edition of the guide, rebuilt against the primary literature, with three corrections substantial enough to change how these compounds should be judged.
What's Inside
Written for anyone being sold these four compounds as SARMs who wants the evidence graded honestly rather than marketed to, and for coaches fielding questions about Cardarine and MK-677. It assumes you can tell the difference between a mouse study and a human trial, and that any decision here involves baseline bloodwork and a clinician. It is a scientific reference rather than a protocol, and it corrects its own first edition in three places where the earlier text was wrong.
No, and the mislabelling hides how different they are. MK-677 is a growth hormone secretagogue acting at the ghrelin receptor, GHS-R1a. GW-501516, sold as Cardarine, is a nuclear receptor agonist at PPARδ, a transcriptional switch that governs which fuel a cell burns. SR-9009 and SR-9011 are agonists at REV-ERB, the nuclear receptors sitting inside the core circadian clock, and both were built as laboratory tool compounds rather than drug candidates. Because none of them touches the androgen receptor, none suppresses LH or FSH, and no post-cycle protocol applies to any of them, which the original guide got right and is worth restating because it is the thing most often misunderstood about this category. Their evidence bases are nowhere near equal either: MK-677 has multiple double-blind randomised trials including one that ran for two years, GW-501516 has short human lipid trials and nothing else, and SR-9009 and SR-9011 have never been tested in a human being at all. All four sit on the WADA Prohibited List under S4 and are banned in and out of competition, all four are detectable, and none is lawful as a supplement ingredient in India, the EU, the UK, the USA or Australia. Everything sold is supplied for laboratory use, outside any pharmacopoeial quality system, and independent testing has repeatedly found mislabelled content and undeclared substances, which makes identity and purity an unquantified risk sitting on top of the pharmacology. Compare the class properly in the Peptide Database.
It amplifies your own growth hormone pulses rather than replacing them, and that architecture explains both its appeal and its ceiling. MK-677 occupies GHS-R1a, the receptor whose natural ligand is ghrelin, which raises the amplitude of existing GH pulses and lifts hepatic IGF-1. Because the axis keeps its negative feedback, IGF-1 plateaus instead of scaling with dose, which is the structural difference between this and exogenous HGH and the reason the drug cannot be pushed to supraphysiological territory. The trial record is the strongest of the four and also the reason Merck stopped developing it. The two-year randomised trial in older adults found GH secretion roughly doubled, IGF-1 restored to the young adult range and fat-free mass up about 1.1 kg at twelve months against a small loss on placebo, but strength and physical function did not improve, so this is a body-composition signal rather than demonstrated contractile tissue, and a meaningful fraction of it is fluid. The same trial showed fasting glucose rising and insulin sensitivity falling, which is expected, since GH is counter-regulatory to insulin. A separate trial in Alzheimer's disease found no benefit on its cognitive endpoint, so the cognition claim is unsupported. The safety signal that matters most came from a hip fracture recovery trial stopped early for a higher rate of congestive heart failure in the treatment arm, and that needs reading in proportion: those were frail elderly patients with little cardiac reserve, not healthy young lifters, but it establishes that sustained GH axis elevation and the fluid expansion that comes with it can decompensate a heart that is already marginal. Appetite is not a side effect here, it is the receptor doing its job, and it cannot be trained out. On the cancer question the guide is deliberately careful: IGF-1 in the upper normal range is associated with certain cancers in observational data, which is reason enough to avoid this with a personal or strong family cancer history, but it is not a demonstrated causal effect of raising IGF-1 pharmacologically and no trial has been long enough to settle it. Glucose, insulin, HbA1c, IGF-1, ApoB and blood pressure are the markers that decide whether this is defensible, so build the panel with the Blood Test Selector and read it with the Bloodwork Analyzer.
Because of what the rodent carcinogenicity programme found, and the original guide described those findings incorrectly. The earlier version said tumours occurred only at excessively high doses over prolonged periods. The two-year rat and mouse studies reported tumours across an unusually broad set of tissues including liver, stomach, tongue, skin, bladder, thyroid, testes, ovaries and uterus, in both species and both sexes, and at every dose tested including the lowest. That is the correction, and it matters because it means no no-observed-adverse-effect level was ever established, so there is no identified exposure below which the effect disappears. In toxicology, the absence of a threshold is itself the finding, and anyone repeating the line about massive doses is describing a study that was not run. GSK terminated development around 2006, which is a strong revealed preference from a company walking away from genuinely attractive lipid data, and Health Canada issued a joint public risk communication warning that the compound was being sold online, was never manufactured or distributed by GSK, and had been halted when long-term animal studies produced a variety of cancers. WADA went further and issued a direct public health warning to athletes, which it does not do for most banned substances. The human data that does exist is real but narrow: short Phase II trials in dyslipidaemic patients showed ApoB down, triglycerides down, HDL up and a shift in LDL particle size, all surrogate endpoints measured over a few weeks, with ApoB as the marker worth tracking. The endurance claim is the weakest part of the whole case, because it traces back to a single 2008 mouse paper in Cell, has never been reproduced as a measured performance endpoint in any controlled human trial, and has been marketed to humans for eighteen years without being tested in them. Two further corrections from the original text: the liver concern with this compound is rodent tumours and not hepatotoxicity, since it has not been shown to raise transaminases in humans, and the lipid effect is better described as reduced ApoB than as lowered LDL cholesterol.
Probably not in the form anyone is buying them. Oral bioavailability of SR-9009 is reported at roughly 2% in rodent pharmacokinetic work, with a short plasma half-life, and every published positive result, the fat loss, the lipid change and the increase in running capacity, was produced by injection in mice at exposures far beyond anything a swallowed capsule delivers. Scaling those injected exposures to a human and then pushing them through a route that absorbs about one fiftieth of what is taken does not arrive anywhere near the studied range, and vendor claims that a cyclodextrin carrier or a sublingual preparation solves this have no published pharmacokinetic data behind them. That reframes the user reports rather than contradicting them: the original guide noted the compound feels mild and that nobody should expect dramatic fat loss, which is correct, but the likeliest explanation is not mild efficacy, it is that very little is reaching circulation. The mechanism is also in question, because a 2019 PNAS study found SR-9009 still reduced cell viability and rewired metabolism in cells engineered to lack both REV-ERBα and REV-ERBβ, leading its authors to conclude that the compound's effects cannot be used as a proxy for REV-ERB activity. Off-target activity of unidentified origin is not reassuring in a molecule with zero human data. SR-9011 is a structural analogue from the same series with an even thinner record, no independent pharmacokinetic characterisation and the same problem, so there is no basis on which to prefer it or to dose it. The honest verdict in the guide is that these two are probably the least dangerous of the four and almost certainly for the wrong reason, which leaves the real exposure as an unregulated capsule whose actual contents are unverified, carrying whatever risk those contents carry. Stacking makes that worse rather than better, since combining two compounds with no human interaction data compounds the uncertainty instead of averaging it, which is why the guide audits each of the original stack suggestions individually. Check any combination against the Peptide Stack Builder before assuming a rationale is evidence.
The full guide covers the receptor classification table, the complete signalling diagrams for each compound, the whole human trial record for MK-677, the dosage evidence review auditing every original figure against the literature, the carcinogenicity dossier in full, the head-to-head comparison matrix, the audit of all five original stack recommendations, a sequential decision framework, the monitoring panel with timing and action thresholds, troubleshooting and fifteen references. Download the PDF for the complete reference.
This page and the full guide are for educational and harm reduction purposes only. They are not medical advice and do not establish any clinician relationship. None of the four compounds described is approved for human use in any jurisdiction, two were abandoned by their developers on safety grounds, and all four are prohibited in sport at all times under WADA S4. Material sold online sits outside any pharmaceutical quality system, so its identity, purity and content cannot be assumed. Nothing here is a recommendation to obtain or use any of them. Adults 18 and over only, and anyone considering these compounds should do so only under the supervision of a qualified physician with full baseline investigations in hand.
No. It is a growth hormone secretagogue acting at the ghrelin receptor, it does not bind the androgen receptor, and it does not suppress LH or FSH, so no post-cycle protocol applies.
Not on the available evidence. Rodent tumours appeared at every dose tested, so no threshold was ever established, which means there is no identified exposure below which the effect disappears.
Oral absorption is around 2% in rodent data, and every positive published result came from injection in mice. The capsule may also not contain what the label claims.
It raised fat-free mass by roughly 1.1 kg over a year in the two-year trial, but a meaningful fraction of that is fluid and strength and physical function did not improve.
This guide is for educational purposes only and is not medical advice.
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