Skip to content

Shop
Scholar
Lab Results
Learn
Vote
Forum
About

Search Kodiac

Sign in Sign up Account

Author: kodiac

Pindolol

Plain-language summaryIntrigue 48 / 100

Pindolol is an old beta-blocker, FDA-approved in 1982, that lowers blood pressure by quieting the heart. What makes it interesting outside cardiology is a side activity: it binds tightly to a serotonin receptor (5-HT1A) that normally throttles serotonin release. By turning off that throttle alongside an SSRI antidepressant, pindolol was hypothesized to make the SSRI kick in faster (days rather than weeks). Trials produced mixed results, with some studies showing accelerated response in depression and others showing nothing. It is still used occasionally in psychiatry as an SSRI booster, but never became standard practice. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Our opinion on this compoundNiche research probe

37/100

Old beta-blocker with real 5-HT1A probe value, but inconsistent clinical signal limits excitement

Look, pindolol is one of those compounds where the mechanism is more interesting than the compound itself. Approved for hypertension in 1982, it spent years as a fairly unremarkable non-selective beta-blocker until researchers noticed something: it binds 5-HT1A receptors with real affinity (Ki around 50 nM) and acts as a partial agonist there. That property got it drafted into psychiatric research as an SSRI augmentor in the 1990s, and for a while it was genuinely intriguing.

The hypothesis was elegant. SSRIs lose their first two weeks to autoreceptor-mediated negative feedback at the raphe. Add a 5-HT1A partial agonist like pindolol, and you desensitize those presynaptic autoreceptors faster, in theory compressing the latency to antidepressant effect. Multiple placebo-controlled trials tested this through the late 1990s and into the 2000s. Some showed a real 1-2 week acceleration. Others did not. The meta-analyses are frustrating reading: positive signal on onset, weaker or null signal on overall efficacy. That inconsistency is the core problem with this compound as a research target, and we think it explains why the field mostly moved on.

Where pindolol still earns its place in a serious library is as a probe. Its specific combination of beta-blockade plus 5-HT1A partial agonism is hard to replicate with other tools. If you’re running mechanistic work on presynaptic serotonin autoreceptor desensitization, or trying to parse the cardiovascular from the serotonergic components of a drug interaction, pindolol gives you a handle thats difficult to replace. Its been called the canonical 5-HT1A binding beta-blocker in mechanism studies for good reason. Buspirone is more selective at 5-HT1A but lacks the beta component entirely. That combination makes pindolol genuinely useful for dissecting receptor contributions in mixed-pharmacology contexts.

What we dont love: the SSRI augmentation question is basically settled as disappointing, the compound is old enough that most interesting questions about it have been asked, and the short half-life (3-4 hours) is a practical nuisance in research designs. Its not a novel mechanism, not a novel compound, and the translational arrow from preclinical to clinical is pointing in different directions depending on which trial you read.

Honestly, if youre building a research program around serotonin autoreceptor biology and need a pharmacological tool with a specific dual profile, pindolol is worth having. As a primary research target in its own right? The case is thin. The probe utility is real but narrow, and the clinical inconsistency means the translational story never really closed.

Novelty

20

Mechanism promise

42

In-category differentiation

35

Evidence quality

45

Translational signal

35

Research bench value

52

Rationale Pindolol scores as a niche probe because its 5-HT1A autoreceptor work is genuinely useful for serotonin pharmacology, but the compound is a 1982 FDA approval with mixed augmentation trial data; bench utility saves it from obscurity, novelty and translational inconsistency drag the overall down.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Non-selective beta-adrenergic antagonist with 5-HT1A partial agonism

A non-selective beta-blocker with intrinsic 5-HT1A partial agonism; investigated as an SSRI augmenting agent.

Abstract

Pindolol (1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-ol; CAS 13523-86-9; molecular formula C14H20N2O2; molecular weight 248.32) is a non-selective beta-adrenergic antagonist with intrinsic sympathomimetic activity (partial agonism) and 5-HT1A partial agonism, approved by the FDA in 1982. The compound’s distinguishing pharmacological feature in psychiatric research is high-affinity 5-HT1A binding (Ki approximately 50 nM) with partial agonist activity at presynaptic autoreceptors; concurrent administration with an SSRI desensitizes the autoreceptor more rapidly than the SSRI alone, hypothetically accelerating the antidepressant response. Multiple placebo-controlled trials in the 1990s and 2000s reported faster onset (1 to 2 weeks shorter latency) but inconsistent overall efficacy improvement. Plasma half-life is 3 to 4 hours; metabolism is hepatic. Approved indications in cardiology include hypertension and angina; the SSRI augmentation use remains off-label. Used as the canonical 5-HT1A binding beta-blocker in mechanism studies.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-257Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Clonidine

Plain-language summaryIntrigue 60 / 100

Clonidine is a 1960s blood-pressure drug (sold as Catapres) that turned out to be unexpectedly versatile. It works by activating alpha-2 adrenergic receptors in the brainstem, dampening the sympathetic nervous system, the body’s stress response. That single mechanism explains why it lowers blood pressure, blunts opioid withdrawal symptoms, calms tics in Tourette syndrome, and reduces hyperactivity in ADHD (often as a non-stimulant alternative or add-on to stimulants in children). It is also used to manage hot flashes and as a sedating premedication. The drug is cheap, generic, and well-characterized, with sedation and rebound hypertension on abrupt discontinuation as the main downsides. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Our opinion on this compoundResearch workhorse

45/100

Prototype alpha-2 agonist with real bench utility but essentially zero research novelty

Look, clonidine is not a research compound in any contemporary sense of the word. Boehringer Ingelheim synthesized it in the 1960s looking for a nasal decongestant, stumbled onto a central antihypertensive, and the FDA approved it in 1974. That backstory tells you a lot about where this thing sits in 2025: its mechanism was characterized before most of today’s investigators were born, and the pharmacology has not moved since.

The mechanism is presynaptic alpha-2A autoreceptor activation in the locus coeruleus, which dials down central noradrenergic tone. Secondary imidazoline I1 activity contributes to the blood pressure effect. Both of those stories are closed chapters in the literature. Theres nothing here that opens a new question; every pathway clonidine touches has been characterized to death, and the interesting molecular biology has moved to more selective tools. Dexmedetomidine is far more alpha-2A selective. Guanfacine has a cleaner CNS profile and is now the preferred agent for ADHD in most treatment algorithms. In differentiation terms, clonidine is the prototype that got superseded.

Where we do give clonidine some credit is bench utility. It remains the canonical alpha-2 reference standard for studies of noradrenergic regulation, locus coeruleus physiology, and sympathetic nervous system modulation. If you’re designing a study that needs a clean alpha-2 agonist as a positive control or pharmacological probe, clonidine is still what most labs reach for, partly because the literature comparator base is enormous. The PTSD-associated hyperarousal work, particularly the fear consolidation studies out of Pitman and Cahill’s groups, used clonidine as the reference intervention precisely because any new agent has to beat a known standard. That kind of indispensable-comparator role keeps the bench value score from cratering.

The translational and evidence scores are the only numbers that look strong here, and honestly they should, because this is an approved drug with decades of clinical use across four labeled indications. The rebound hypertension on abrupt discontinuation is one of the best-characterized discontinuation effects in all of pharmacology. But evidence quality for a research library score is about how much we’ve learned, not how much we’ve confirmed; at this point clonidine is all confirmation, no discovery.

We think this compound belongs in the library as a reference entry, not as something an investigator would build a program around in 2025. The score of 45 reflects that: real clinical and bench-utility credit, close-to-zero novelty and mechanism credit. Use it as the comparator arm, not the experimental arm.

Novelty

18

Mechanism promise

28

In-category differentiation

35

Evidence quality

78

Translational signal

72

Research bench value

65

Rationale Clonidine scores moderate overall on the strength of its well-validated clinical record and genuine utility as the reference alpha-2 agonist in noradrenergic research, but novelty and mechanism scores drag hard because this is a 1960s compound with a fully mapped single-receptor mechanism; more selective successors like dexmedetomidine and guanfacine have largely displaced it in both clinic and bench contexts.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Central alpha-2 adrenergic agonist

An imidazoline alpha-2 adrenergic receptor agonist; an antihypertensive repurposed for ADHD, opioid withdrawal, and Tourette syndrome.

Abstract

Clonidine (N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine; CAS 4205-90-7; molecular formula C9H9Cl2N3; molecular weight 230.10) is an imidazoline alpha-2 adrenergic agonist developed at Boehringer Ingelheim in the 1960s and approved by the FDA in 1974 under the trade name Catapres. The compound activates presynaptic alpha-2A adrenergic autoreceptors in the locus coeruleus, reducing central noradrenergic outflow and producing centrally mediated reductions in sympathetic tone, blood pressure, and heart rate. Secondary imidazoline I1 receptor activity contributes to the antihypertensive effect. Plasma half-life is 12 to 16 hours; renal excretion is the principal clearance pathway. Approved indications include hypertension, ADHD (extended-release Kapvay), opioid withdrawal, and Tourette syndrome; off-label use in insomnia, hot flashes, and PTSD-associated hyperarousal. Rebound hypertension on abrupt discontinuation is a characteristic adverse effect. The compound is widely used in academic neuroscience as the prototype alpha-2 agonist for studies of noradrenergic regulation.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-258Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Guanfacine

Plain-language summaryIntrigue 62 / 100

Guanfacine is a more selective cousin of clonidine, originally a blood-pressure drug (Tenex) that found a second life as a non-stimulant ADHD medication (Intuniv, extended-release form). Where clonidine hits all three alpha-2 receptor subtypes broadly, guanfacine prefers the alpha-2A subtype, which is concentrated in the prefrontal cortex (the executive-function part of the brain). Activating it there appears to strengthen working memory and reduce impulsivity, which is the rationale for ADHD use. It is less sedating than clonidine at equivalent effect and is FDA-approved for ADHD in children and adolescents. Often combined with stimulants when stimulants alone are insufficient. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Our opinion on this compoundEstablished, active research

51/100

Canonical alpha-2A PFC probe with mature ADHD evidence; novelty is low, precision is high

Look, guanfacine is a genuinely useful compound and we’re glad it’s in the library, but let’s be honest about where it sits in the research landscape. This is a 1970s Sandoz molecule, FDA-approved for hypertension in 1986, with the ADHD indication following in 2009 as Intuniv. The core chemistry and pharmacology have been understood for decades, and there’s no mystery left in the primary mechanism.

What keeps it interesting is the alpha-2A subtype selectivity story. Clonidine predates guanfacine and acts across 2A, 2B, and 2C subtypes with less discrimination; guanfacine runs roughly 25-fold selective for 2A over the other subtypes. That matters because alpha-2A receptors dominate the prefrontal cortex, where adrenergic tone directly modulates working memory and executive function through post-synaptic signaling that reduces cAMP and increases the signal-to-noise ratio of PFC pyramidal neurons. Amy Arnsten’s work at Yale is the anchor here, and her group has done the most rigorous mapping of how alpha-2A agonism strengthens PFC network firing without the sedation you get from clonidine at comparable doses.

As a bench tool, guanfacine is the reference compound for alpha-2A pharmacology in the PFC. If you’re running experiments on stress-induced working memory impairment, age-related cognitive decline, or the adrenergic circuitry underlying impulsivity, guanfacine is your cleanest available probe. That’s a real point in its favor, and we score bench utility accordingly.

The evidence base is mature and solid. Multiple phase 3 RCTs in pediatric ADHD, a clean safety profile relative to stimulant alternatives, and well-replicated preclinical work in non-human primates and rodent models going back decades. That said, the effect sizes in ADHD are modest compared to stimulants, and the translational signal, while real and confirmed, doesnt represent a paradigm-defining clinical outcome. It’s a solid, confirmed, specific effect; not a revolutionary one.

We think the honest limitation here is novelty. There’s not much territory left to explore in the core mechanism. New applications do surface, including PTSD (guanfacine for hyperarousal, with some promising small trials out of groups like Pitman’s at Harvard) and emerging work on stress-sensitization in substance use disorders, and those angles give the score a small lift. But for most bench programs that dont specifically need an alpha-2A probe, guanfacine isnt the compound that’s going to define a new research direction. It does a specific job extremely well, and if that job is yours, it belongs in your toolkit.

Novelty

20

Mechanism promise

42

In-category differentiation

58

Evidence quality

73

Translational signal

67

Research bench value

63

Rationale Guanfacine earns on differentiation and evidence as the canonical alpha-2A selective agonist and an FDA-approved compound with replicated ADHD trials, but a 1970s mechanism and fully mapped pharmacology hold novelty and mechanism scores low, producing a mid-tier overall that reflects its value as a precision tool rather than a research frontier.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Selective alpha-2A adrenergic agonist

A selective alpha-2A adrenergic agonist; an antihypertensive repurposed as a non-stimulant ADHD treatment with greater alpha-2A selectivity than clonidine.

Abstract

Guanfacine (N-{[2-(2,6-dichlorophenyl)acetyl]amino}guanidine; CAS 29110-47-2; molecular formula C9H9Cl2N3O; molecular weight 246.10) is a selective alpha-2A adrenergic agonist developed at Sandoz in the 1970s and approved by the FDA in 1986 under the trade name Tenex (immediate release) and 2009 as Intuniv (extended release for ADHD). Distinct from clonidine by greater alpha-2A subtype selectivity (approximately 25-fold over alpha-2B and alpha-2C); the alpha-2A subtype predominates in the prefrontal cortex where it modulates working memory and executive function, supporting the cognitive enhancement seen in ADHD. The CNS-prefrontal cortex effect is more pronounced than the cardiovascular effect at clinical ADHD doses. Plasma half-life is approximately 17 hours, supporting once-daily dosing in the ER formulation. Renal excretion is the principal clearance pathway. Approved for hypertension and (Intuniv) ADHD in children and adolescents. Used as the canonical alpha-2A selective agonist in prefrontal cortex pharmacology and ADHD research.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-259Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Ostarine (MK-2866)

Our opinion on this compoundEstablished workhorse

39/100

Prototype SARM with the strongest human trial record in its class, but a failed phase 3 and a crowded successor field cap its research appeal

Look, Ostarine occupies a weird position in the SARM landscape. It was the first non-steroidal aryl propionamide to reach serious clinical evaluation, the proof-of-concept that tissue-selective androgen receptor agonism was achievable without the full androgenic liability of testosterone. That mattered enormously in 2005. In 2026, its prototype status is mostly a historical footnote.

The mechanism story is genuinely elegant, and we should credit it. Differential coactivator and corepressor expression across tissue types means the same ligand-receptor complex produces different conformational changes in skeletal muscle versus prostate. Ostarine exploits that. The pharmacology is clean, oral bioavailability is high, and the 24-hour half-life supports once-daily dosing in preclinical protocols. For a researcher setting up a model of tissue-selective AR biology, it remains a credible probe. Thats the bench value argument and its real, if modest.

The clinical record is where things get complicated. Phase 2 data from the GTx cachexia and stress urinary incontinence programs showed genuine lean mass accretion and some bone density signal. Those results were real enough to license to Merck and push to phase 3. Then the POWER trial happened. In 2013, enobosarm failed to meet its primary endpoints in cancer-associated muscle wasting despite what looked like a clean phase 2 story. The failure wasnt a mechanism disproof, but it did deflate the primary translational thesis and the compound has sat in a regulatory limbo ever since, no approval pathway, WADA-banned, and commercially gray-market.

What we dont like: the class has moved on. LGD-4033 hits harder. RAD-140 has a better anabolic-to-androgenic ratio in most model systems. Newer investigational SARMs have more interesting selectivity profiles and some have more recent human PK data. Ostarine is the weakest member of a class that now has stronger options, which tanks its differentiation score significantly. You can argue it has the cleanest human safety profile because its the least potent, but that argument only holds if you actually want a weak SARM, which most investigators don’t.

Where Ostarine still earns its place in a research library is as a reference comparator. Any serious SARM study needs a benchmark, and Ostarine is the most characterized option for that role. The hepatic enzyme elevation and HPG suppression signals at supratherapeutic doses are documented well enough to design around. For comparative mechanistic work on AR coactivator biology, the existing PK and safety data saves setup time. Honestly though, if your research question is about anabolic selectivity at the frontier of the field, there are better compounds to anchor a program around right now.

Novelty

22

Mechanism promise

42

In-category differentiation

32

Evidence quality

58

Translational signal

42

Research bench value

48

Rationale Ostarine scores reasonably on evidence because it is the most human-trialed SARM by a wide margin, but novelty and differentiation drag the composite down hard: the compound is 20-plus years old, the tissue-selective AR mechanism is now textbook, and the 2013 POWER trial failure for cancer cachexia weakened the primary translational story. More potent and more selective SARMs have entered the literature since, leaving Ostarine as a historical reference compound rather than a live frontier target.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Selective androgen receptor modulator (non-steroidal)

A selective androgen receptor modulator developed for cachexia and muscle wasting; the prototype SARM and the most thoroughly characterized in human trials.

Abstract

Ostarine (Enobosarm, MK-2866, GTx-024; CAS 841205-47-8; molecular formula C19H14F3N3O3; molecular weight 389.33) is a selective androgen receptor modulator (SARM) developed at GTx Inc. (later licensed to Merck). The compound is a non-steroidal aryl propionamide that binds the androgen receptor (AR) with tissue-selective agonism: full agonist activity in skeletal muscle and bone, partial or absent activity in prostate and sebaceous glands. The selectivity arises from tissue-specific differences in AR coactivator and corepressor expression and from differential conformational induction by non-steroidal versus steroidal ligands. Phase 2 trials in cancer cachexia and stress urinary incontinence demonstrated lean body mass gains and bone density improvements, but a definitive phase 3 trial in cancer cachexia (POWER) failed to meet primary endpoints in 2013. The compound retains significant academic interest as a SARM prototype and is widely used recreationally (banned by WADA in sport) despite no regulatory approval. Plasma half-life is approximately 24 hours; oral bioavailability is high. The principal safety concerns are hepatic enzyme elevation and HPG axis suppression at supratherapeutic doses.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-261Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Yohimbine

Plain-language summaryIntrigue 55 / 100

Yohimbine is an alkaloid extracted from the bark of an African tree (Pausinystalia johimbe), used historically as an aphrodisiac. Pharmacologically it is an alpha-2 receptor blocker, which means it does the opposite of clonidine: it ramps up the sympathetic nervous system, raising noradrenaline release. At low doses it can produce alertness, anxiety, and a small erectile-function benefit; at higher doses it triggers panic-like states and is used in research as a deliberate panic challenge. Sold widely as a fat-loss and pre-workout supplement, with mixed clinical evidence. The pressor and anxiogenic effects make it dangerous for people with cardiovascular disease or anxiety disorders. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Our opinion on this compoundNiche research probe

41/100

The canonical alpha-2 pharmacological probe; low novelty but durable bench utility for noradrenergic research programs

Look, yohimbine isn’t a compound you discover. It’s one you already know. The alpha-2 adrenergic antagonist literature is old enough to be cited in textbooks that are themselves dated, and yohimbine sits at the center of that literature as the reference standard. That’s both its greatest asset and the reason its overall research merit sits in the low 40s.

The mechanism is textbook. Presynaptic autoinhibition blockade, increased noradrenergic outflow, downstream cascade of blood pressure elevation, anxiety, tachycardia, mydriasis. Nobody is writing a grant to characterize the mechanism of yohimbine. The pharmacology has been settled for decades. What keeps it alive is the same thing that keeps ketamine alive after decades of use: sometimes you need the probe more than you need the novelty.

Where yohimbine earns its keep is the panic disorder provocation paradigm. Charney’s group at Yale, and multiple independent replications, have used IV yohimbine challenges to map noradrenergic dysregulation in PTSD, panic disorder, and stress-sensitization models. The selectivity profile is clean, roughly 50-fold alpha-2 over alpha-1 (Ki approximately 1 to 5 nM versus alpha-1), and the short plasma half-life of around 0.6 hours gives investigators temporal control that a longer-acting compound would undermine. That’s genuine bench-to-clinic utility. It doesnt generate new biology, but it lets you interrogate existing biology with real precision.

The therapeutic end is considerably weaker. The erectile dysfunction angle, which accounts for most of its commercial footprint, has an evidence base that consistently underdelivers. Multiple controlled trials show inconsistent effects and modest effect sizes that wouldn’t satisfy a high-standard systematic review. The secondary 5-HT1A partial agonism at around 100 nM adds theoretical texture but doesn’t meaningfully shift the clinical picture.

What we like: the compound is well-characterized, dosing windows and washout periods are firmly established across decades of human pharmacology studies, and purity from pharmaceutical-grade suppliers is reliable. If your lab is running any kind of noradrenergic activation study or a sympathetic challenge protocol, yohimbine is still the tool you reach for. thats not nothing.

What we don’t like: there is essentially nothing new here. No serious group is exploring genuinely novel indications, the mechanism space is fully occupied, and sourcing from OTC channels introduces purity variance that can undermine experimental control. For investigators specifically working on noradrenergic circuits or panic neurobiology, yohimbine is necessary. For everyone else, it’s a reference standard worth knowing and not much more.

Novelty

20

Mechanism promise

28

In-category differentiation

42

Evidence quality

58

Translational signal

48

Research bench value

68

Rationale Yohimbine scores low on novelty and mechanism freshness because the alpha-2 antagonism story is textbook-settled, but its bench value lifts the overall via genuine indispensability in noradrenergic and panic-biology provocation paradigms. No scheduling or category cap applies; the 41 reflects a compound that earns its place as a probe, not as a discovery target.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Selective alpha-2 adrenergic antagonist

An indole alkaloid alpha-2 adrenergic antagonist from Pausinystalia johimbe; the canonical pharmacological probe for noradrenergic activation.

Abstract

Yohimbine (17-alpha-hydroxy-yohimban-16-alpha-carboxylic acid methyl ester; CAS 146-48-5; molecular formula C21H26N2O3; molecular weight 354.45) is an indole alkaloid isolated from the bark of Pausinystalia johimbe (Rubiaceae) and from Rauwolfia species. The compound is a selective alpha-2 adrenergic antagonist (Ki approximately 1 to 5 nM) with secondary 5-HT1A partial agonism (Ki approximately 100 nM); selectivity for alpha-2 over alpha-1 is approximately 50-fold. Pharmacologically, yohimbine increases central noradrenergic outflow by blocking presynaptic autoinhibition, producing anxiety, increased blood pressure, mydriasis, and tachycardia. Used in clinical research as a provocation test for panic disorder (where vulnerability to alpha-2 antagonism predicts panic susceptibility) and as a positive control in studies of noradrenergic regulation. Folk use as an aphrodisiac for erectile dysfunction has limited supporting evidence. Plasma half-life is approximately 0.6 hours. Used as the canonical alpha-2 antagonist in academic pharmacology.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-260Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Ligandrol (LGD-4033)

Our opinion on this compoundEstablished, active research

39/100

Canonical high-affinity SARM with real phase 1 data, but mechanistically mature and clinically stalled

Look, there’s a version of this compound that sounds exciting on paper: sub-nanomolar AR affinity, tissue selectivity, phase 1 lean-mass data, and a development history at two serious pharmaceutical shops. That version isn’t wrong. But we’re scoring research merit in 2026, and the honest picture of LGD-4033 is a mature SARM with a mostly settled mechanism in a class that has been chasing the same tissue-selectivity promise for twenty years without a single approved drug to show for it.

The mechanism itself, tissue-selective androgen receptor agonism via a non-steroidal ligand, is real and reasonably well understood. LGD-4033 binds AR at roughly 1 nM (Ki), several-fold tighter than ostarine, and that affinity advantage is why it became the canonical reference compound for high-affinity SARM work. If your research question is specifically about the pharmacology of high-affinity partial AR agonism, theres a legitimate reason to reach for this molecule. That single-axis differentiation is real and we credit it in the bench value and differentiation scores. But it doesn’t change the fact that the mechanism hasn’t evolved, its single-receptor agonism in a class that has been around long enough that Ligand Pharmaceuticals itself spun the asset out to Viking Therapeutics to pursue it further.

The clinical story is complicated. The Bhasin phase 1 data (0.1-1 mg, 21 days, healthy males) is genuinely clean: dose-dependent lean body mass gains, no significant prostate signal, reasonable tolerability. Thats a real signal. The problem is what came after. The VK5211 hip fracture program has had intermittent readouts and hasn’t generated the sort of decisive phase 2 data that would make this compound compelling to follow right now. HPG axis suppression at the higher dose tier is a liability the class has never fully escaped, and recreational use at 5-10 mg (supratherapeutic by clinical standards) has muddied the human data pool considerably.

What we like: the canonical status matters. LGD-4033 is the molecule you’d reach for if you need a high-affinity SARM probe to interrogate AR-dependent pathways in vitro or in a clean animal model. The pharmacokinetics (24-36 hour half-life) are researcher-friendly. The phase 1 dataset is honest and reproducible. What we don’t like: the class promise has underdelivered for two decades, the VK5211 program hasn’t produced a decisive signal, and there’s genuinely nothing novel happening mechanistically. If you’re not specifically studying SARMs, there’s little here that you can’t get from a better-characterized or more clinically advanced tool. Score it accordingly: useful in the right context, not a priority pick outside of it.

Novelty

28

Mechanism promise

30

In-category differentiation

45

Evidence quality

45

Translational signal

42

Research bench value

58

Rationale LGD-4033 scores modestly on novelty and mechanism because selective AR agonism is a mature, well-trodden strategy, but its canonical status as the reference high-affinity SARM and solid phase 1 lean-mass data keep it out of the workhorse or established-mature basement. The intermittent phase 2 (VK5211) trajectory and HPG suppression signal cap the translational score.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Selective androgen receptor modulator

A non-steroidal SARM developed for muscle wasting; one of the more potent SARMs at AR binding.

Abstract

Ligandrol (LGD-4033, VK5211; CAS 1165910-22-4; molecular formula C14H12F6N2O; molecular weight 338.25) is a non-steroidal SARM developed by Ligand Pharmaceuticals (later out-licensed to Viking Therapeutics as VK5211). The compound is a high-affinity AR ligand (Ki approximately 1 nM, several-fold higher affinity than ostarine) with tissue-selective agonism similar to other SARMs. Phase 1 trials in healthy male volunteers demonstrated dose-dependent increases in lean body mass at doses of 0.1 to 1 mg daily over 21 days, with no significant prostate effects but with HPG axis suppression at the higher dose tier. Subsequent phase 2 development (VK5211) targeted hip fracture recovery; results have been intermittent. Plasma half-life is approximately 24 to 36 hours. The compound is widely used recreationally at supratherapeutic doses (5 to 10 mg) and is banned by WADA. Used as the canonical high-affinity SARM in mechanism studies.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-262Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Testolone (RAD-140)

Our opinion on this compoundEstablished, active research

50/100

Highest-potency SARM with a real clinical trajectory in breast cancer, but mechanism maturity limits ceiling

RAD-140 is probably the most potent SARM in the research toolkit, and that does matter for how you use it on the bench. With a Ki around 7 nM and intrinsic activity that in some preclinical models exceeds testosterone propionate at equivalent molar doses, it’s not a subtle tool. The selectivity profile – meaningful anabolic activity with reduced androgenic effects in prostate tissue compared to steroidal androgens – is what got Radius Health interested in the first place, and it’s still the core value proposition.

The breast cancer angle is where things get genuinely interesting. AR-positive metastatic breast cancer is a real clinical problem with limited options, and the phase 1 data in postmenopausal women did show dose-dependent AR pathway engagement. The program moved into phase 2, which puts RAD-140 in a much smaller club than most SARMs that never get near a clinic. Thats worth noting when you’re assessing the translational signal here.

So why a 50? Honestly, the SARM mechanism is the limiting factor. Tissue-selective AR agonism is well-understood at this point – the co-activator recruitment story, the differential downstream signaling in muscle versus prostate, the axis suppression trade-offs. None of that is new. And the SARM space has been actively researched for long enough that what once felt genuinely novel now feels like a crowded field. RAD-140 is the highest-potency member of an increasingly mature class.

The evidence situation is better than most SARMs but still limited by phase 2 standards. Phase 1 data really just establishes that the target is engaged and acute tolerability is acceptable. We dont yet have efficacy data that would move a serious investigator from “interesting” to “important.” Long-term safety is a genuine unknown, HPG suppression is a real concern at pharmacological doses, and hepatic enzyme elevation signals at supratherapeutic exposures add caution flags for extended study designs.

As a bench tool, RAD-140 is actually quite useful. If you’re studying AR selectivity, differential co-activator biology, or SARM-class pharmacokinetics – that approximately 60-hour half-life is unusually long for the class – it gives you a high-signal probe. The widespread recreational use, frustrating from a regulatory standpoint, has generated a substantial body of observational pharmacokinetic data that investigators sometimes find valuable for dose-ranging rationale in study design.

We think this sits firmly in established-active territory. The breast cancer indication keeps it clinically relevant and worth watching; the mechanism maturity and evidence ceiling keep it from scoring higher.

Novelty

44

Mechanism promise

48

In-category differentiation

55

Evidence quality

48

Translational signal

50

Research bench value

58

Rationale RAD-140 earns its place as the benchmark high-potency SARM with actual phase 1/2 clinical data in AR-positive breast cancer, but tissue-selective AR agonism is a well-understood mechanism in an increasingly crowded class, and evidence quality stops well short of replicated phase 3 data.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Selective androgen receptor modulator (high-potency)

A potent non-steroidal SARM developed for muscle wasting and breast cancer; one of the highest-potency SARMs by binding affinity.

Abstract

Testolone (RAD-140; CAS 1182367-47-0; molecular formula C20H16ClN5O2; molecular weight 393.83) is a non-steroidal SARM developed by Radius Health for muscle wasting and (subsequently) AR-positive metastatic breast cancer. The compound is a high-potency AR ligand (Ki approximately 7 nM with high intrinsic activity) and a tissue-selective agonist; preclinical studies demonstrated anabolic activity in skeletal muscle exceeding that of testosterone propionate at equivalent molar doses, with reduced prostate effects. Phase 1 trials in postmenopausal women with metastatic breast cancer demonstrated dose-dependent AR pathway engagement; the program was advanced into phase 2. The compound is among the most widely used SARMs recreationally despite no regulatory approval. Plasma half-life is approximately 60 hours, supporting once-daily dosing. The principal safety concerns are HPG axis suppression and hepatic enzyme elevation at supratherapeutic doses; long-term safety data are absent.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-263Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Cardarine (GW-501516)

Our opinion on this compoundNiche research probe

43/100

Canonical PPAR-delta probe with real bench utility and a decisively dead translational path

Look, GW-501516 occupies a genuinely unusual position in the research compound landscape. It’s not a novel discovery and it’s not a failed hypothesis. It’s a tool with real utility that was abandoned for safety reasons, and understanding that distinction matters for how you think about it.

The mechanism is legitimate. PPAR-delta activation in skeletal muscle drives fatty acid oxidation and mitochondrial biogenesis through the PGC-1alpha axis. GSK’s phase 2 work in dyslipidemia showed real changes: HDL going up, triglycerides coming down. The biology is coherent and the compound does what it’s supposed to do. Thats actually part of what makes the carcinogenicity story so uncomfortable: this isn’t a failed mechanism, it’s a working mechanism in a compound that accelerates tumor growth at the same time.

The 2007 carcinogenicity data is what ended the GSK program. Long-term studies in both rats and mice showed dose-dependent tumor formation across multiple organ systems at every dose level tested. Not a marginal finding in one tissue at high dose: multiple tissues, multiple species, dose-response fully intact. WADA banned it in 2009. The recreational community largely ignored both of these facts, which is its own kind of signal about how people evaluate uncomfortable data when a compound does something they want it to do.

Here’s what keeps GW-501516 on the map for serious researchers: it remains the most well-characterized PPAR-delta agonist available for academic metabolic research. If you want to study PPAR-delta biology, fat oxidation pathways, mitochondrial biogenesis signaling, or the relationship between endurance capacity and substrate utilization, GW-501516 is still the reference compound. There arent many clean alternatives with comparable depth of characterization. That’s real bench value, and we give it credit for that specifically.

What it doesn’t have is a translational future. The clinical development program is dead and is not coming back. Any research program using this compound has to be oriented toward mechanistic probe work, not toward a clinical endpoint. That’s a legitimate scientific purpose, and there are genuine questions about PPAR-delta biology worth pursuing. But the constrained scope is real, and it shows up in the score.

We think the honest framing is: useful tool, dangerous compound, dead translational path. For a researcher working on PPAR-delta biology, muscle metabolism, or mitochondrial signaling in skeletal tissue, this compound is worth understanding. For anyone thinking about a translational arc or a human-facing program, there is nothing here to build toward. The score reflects that balance: a solid niche probe with no credible exit toward clinical relevance.

Novelty

30

Mechanism promise

38

In-category differentiation

58

Evidence quality

50

Translational signal

30

Research bench value

62

Rationale GW-501516 earns its differentiation and bench-value scores as the reference PPAR-delta agonist with genuine phase 2 lipid data, but tanks on translational signal and novelty because the clinical program is permanently closed by dose-dependent multi-organ carcinogenicity across both rodent species; no structural cap applies because the mechanism is intact and validated, only the safety profile is fatal.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

PPAR-delta agonist (not a SARM)

A PPAR-delta agonist developed for dyslipidemia; widely used recreationally as an endurance enhancer despite cancer findings in long-term rodent studies.

Abstract

Cardarine (GW-501516, Endurobol; CAS 317318-70-0; molecular formula C21H18F3NO3S2; molecular weight 453.50) is a peroxisome proliferator-activated receptor delta (PPAR-delta) agonist developed at GlaxoSmithKline for dyslipidemia. The compound is not a SARM; it is grouped with SARMs in popular discourse owing to similar recreational use patterns. PPAR-delta activation in skeletal muscle increases fatty acid oxidation, mitochondrial biogenesis, and endurance capacity. Phase 2 trials in dyslipidemia demonstrated favorable lipid profile changes (HDL increase, triglyceride decrease). Development was halted by GSK in 2007 after long-term carcinogenicity studies in rats and mice showed dose-dependent tumor formation in multiple organs at all dose levels tested. The compound retains research utility as the canonical PPAR-delta agonist for academic metabolic research and is widely used recreationally despite the carcinogenicity signal; banned by WADA. Plasma half-life is approximately 24 hours.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-265Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Andarine (S-4)

Our opinion on this compoundEstablished workhorse

26/100

Superseded prototype SARM with abandoned clinical development and narrow SAR probe utility

Yeah, andarine is historically important and practically irrelevant for most serious research programs right now. It’s the structural parent of the entire aryl propionamide SARM lineage, GTx-007, the compound Dalton’s group at the University of Tennessee used to establish the SARM concept before they handed the baton to ostarine and moved on. That lineage story is genuinely interesting. The compound itself is not.

Here’s the problem: andarine was superseded by its own derivative. Ostarine (enobosarm, GTx-024) exists specifically because S-4’s clinical development hit a wall in the form of that dose-dependent visual disturbance, the yellow-green color tint that appears around 50 mg and above. The mechanism appears to involve non-AR-mediated binding to retinal photoreceptor proteins, and while it reverses on discontinuation, it was clinically unacceptable for any chronic-use indication. GTx didnt abandon S-4 because the AR biology was wrong. They abandoned it because a structurally similar compound without the retinal liability was sitting in the pipeline. That’s not a research compound’s origin story you want to build a program around.

The SARM mechanism itself, tissue-selective AR partial agonism through the propionamide scaffold, is now mature pharmacology. The class has moved past andarine in every meaningful direction. Ostarine went to phase 3 in cancer cachexia and muscle wasting. LGD-4033 has published human PK data. RAD-140 has brain-penetrant properties that open a different set of questions entirely. Andarine is the structural ancestor of all of them, but ancestry doesn’t translate into research utility in 2026.

What we’d actually grant it: the retinal side effect is genuinely undercharacterized. The non-AR mechanism behind the photoreceptor binding is an open question, and if someone wanted to probe SARM off-target effects in visual tissue or build an in vitro assay for retinal safety screening in novel androgen modulators, S-4 is the natural tool. Thats a real research niche. The compound also has reference value in aryl propionamide SAR panels, where having the original scaffold in the comparison set makes mechanistic sense.

But those uses are narrow and specialized. The compound has thin preclinical depth outside the original Dalton program, essentially no clinical data of its own, and competes directly against ostarine in any application where you’d actually want an aryl propionamide SARM. For most research programs, andarine is a historical footnote kept in the library for completeness and lineage documentation. We dont expect it to drive a serious research agenda, and the score reflects that honestly.

Novelty

22

Mechanism promise

28

In-category differentiation

20

Evidence quality

30

Translational signal

22

Research bench value

45

Rationale Andarine scores low primarily because it was actively superseded by its own structural derivative (ostarine) and clinical development was abandoned due to retinal tolerability failure rather than mechanism failure; the aryl propionamide SARM mechanism is now decades-old pharmacology, and the compound has essentially no clinical data and limited research utility beyond SAR reference work and the undercharacterized photoreceptor side effect.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Selective androgen receptor modulator (early-generation)

An early-generation aryl propionamide SARM; the structural lineage compound from which ostarine was derived.

Abstract

Andarine (S-4, GTx-007; CAS 401900-40-1; molecular formula C19H18F3N3O6; molecular weight 441.36) is a non-steroidal aryl propionamide SARM developed by Dalton and colleagues at the University of Tennessee, the structural precursor to ostarine. The compound exhibits tissue-selective AR agonism and demonstrated efficacy in osteoporosis and BPH preclinical models. Notable for a dose-dependent visual side effect: yellow-green tint to vision at doses above approximately 50 mg, attributed to non-AR-mediated effects on retinal photoreceptors and pigments. The visual effect is reversible on discontinuation but proved clinically unacceptable for long-term development; GTx redirected development to ostarine for superior tolerability. Andarine retains research utility as the prototype aryl propionamide SARM and is widely used recreationally despite no regulatory approval. Plasma half-life is approximately 4 hours.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-264Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Stenabolic (SR-9009)

Our opinion on this compoundNiche research probe

51/100

The canonical Rev-erb-alpha probe with genuine circadian-metabolic bench utility but near-zero translational signal

Look, SR-9009 occupies a specific and genuinely useful niche in circadian and metabolic research. It’s the canonical Rev-erb-alpha agonist, which means if you’re building a research program around circadian clock genes and their downstream metabolic effects, this is your compound. That matters. But the score here is held firmly in the low-50s by a set of problems that any serious investigator needs to confront before putting this on the bench.

The mechanism is legitimately interesting. Rev-erb-alpha sits at the intersection of circadian regulation and metabolic gene expression, with downstream effects on fatty acid oxidation pathways, BMAL1/CLOCK transcriptional machinery, and inflammatory gene suppression. The Burris group at Scripps (the same group that developed SR-9009) demonstrated real exercise capacity and body composition effects in mouse models, and the target biology is active enough that independent groups have continued using the compound as a probe to dissect this circuit. That’s the good news.

Here’s the problem: the pharmacokinetics are genuinely rough. Oral bioavailability in rodents is under 5 percent. The Scripps data that generated all the excitement was intraperitoneal. Thats a meaningful caveat for any translational read, and it’s the kind of thing that separates serious preclinical work from the popular hype that followed. You can’t take IP rodent data with a compound this poorly absorbed and draw confident lines toward human biology. There are no human clinical trials for SR-9009. None. The translational gap here is not theoretical, its structural.

What saves SR-9009’s research value is exactly what it was designed for: utility as a tool compound. If you’re studying how Rev-erb-alpha agonism affects lipid catabolism, glucose homeostasis, or the transcriptional output of the circadian clock machinery, SR-9009 is your best available probe. GSK4112 and SR-9011 exist in the same space, but SR-9009 has the most extensive associated literature and remains the reference compound most labs reach for. On that axis alone, it earns its place on a serious research bench.

The evidence base is also concentrated. Burris group papers dominate the foundational claims, with independent work using SR-9009 as a tool rather than actively validating those claims from scratch. Multi-lab preclinical use exists, but the primary efficacy data hasn’t been tested in humans, and the bioavailability issue creates real uncertainty about how much of the rodent signal survives any route-compatible translation attempt. We think SR-9009 is worth having in a library focused on circadian-metabolic biology. It’s a real probe for a real target with active research interest. But dont confuse probe utility with therapeutic candidate status; the score reflects exactly that distinction.

Novelty

50

Mechanism promise

60

In-category differentiation

68

Evidence quality

38

Translational signal

20

Research bench value

70

Rationale SR-9009 scores primarily on differentiation and bench value as the go-to Rev-erb-alpha agonist for circadian biology research, but the combination of no human clinical data, sub-5% oral bioavailability in rodents, and a Scripps-dominated literature base holds the overall score firmly in the low-50s.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

Rev-erb-alpha agonist (not a SARM)

A Rev-erb-alpha agonist developed for circadian and metabolic disorders; popularly grouped with SARMs but mechanistically distinct.

Abstract

Stenabolic (SR-9009; CAS 1379686-30-2; molecular formula C20H24ClN3O4S; molecular weight 437.94) is a synthetic Rev-erb-alpha agonist developed by Burris and colleagues at Scripps Research Institute. Rev-erb-alpha is a nuclear receptor with circadian regulation function; pharmacological agonism shifts metabolic gene expression toward fatty acid oxidation and reduces inflammatory gene transcription. Mouse studies demonstrated improved exercise capacity and body composition with intraperitoneal dosing, generating substantial popular interest. The compound has poor oral bioavailability (less than 5 percent in rodents), making the recreational oral use pattern pharmacologically inconsistent with the published in vivo data. SR-9009 is not approved by any regulatory authority and has no human clinical trial record. Plasma half-life is approximately 4 hours after IP dosing in rodents. Used as the canonical Rev-erb-alpha agonist in academic circadian and metabolic research.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-266Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026

←Previous Page

1 … 64 65 66 67 68 69

Bench-grade research compounds. Cited research. Verified COAs.

kodiac.bio

Explore

Shop
Monographs
Lab Results
About
Affiliate program
Affiliate handbook

Account

Cart
My account

Help

Compliance
Contact

Quarterly dispatch

New batches and new monographs only. Unsubscribe in one click.

Write to us from the contact page to join the list.

Kodiac biolabs sells research compounds for in vitro and in vivo investigative purposes only. Products are not for human or veterinary consumption. Not for medical, diagnostic, or therapeutic use. By using this site you confirm you are acquiring research compounds for research purposes only.

Kodiac biolabs is not affiliated with the U.S. Food and Drug Administration. Products are research reagents, have not been evaluated by the FDA, and are not intended to diagnose, treat, cure, or prevent any disease.

© 2026 Kodiac biolabs LLC. All rights reserved.