Skip to content

Shop
Scholar
Lab Results
Learn
Vote
Forum
About

Search Kodiac

Sign in Sign up Account

Author: kodiac

Gaboxadol (THIP)

Our opinion on this compoundNiche research probe

61/100

The canonical extrasynaptic delta-GABA-A probe; therapeutically abandoned but mechanistically irreplaceable for tonic inhibition research

Look, gaboxadol is a weird one to rate because it exists in two completely separate stories simultaneously. The first story is a clinical failure: Lundbeck and Merck took it through Phase 3 in primary insomnia, watched patients experience disorientation and hallucinations, and pulled the plug in 2007. That story is over. The second story is the interesting one, and its the reason gaboxadol belongs in this library at all.

Here’s the thing about the mechanism. Most GABA pharmacology targets synaptic receptors, the alpha1/2/3-beta-gamma2 isoforms that benzodiazepines and z-drugs hit. Those receptors mediate phasic inhibition, fast transient signals. Gaboxadol does something different: it’s a superagonist at extrasynaptic GABA-A receptors bearing the delta subunit, primarily alpha4-beta3-delta and alpha6-beta3-delta, and those receptors mediate tonic inhibition, the continuous low-amplitude background current that sets the excitability baseline of a neuron. Thats a genuinely different biological variable, and most of the GABA pharmacology toolkit doesn’t let you isolate it cleanly.

We think the differentiation here is underappreciated. Muscimol hits both synaptic and extrasynaptic receptors indiscriminately. DS2, a delta-selective PAM, modulates the receptor but doesn’t agonize it directly. If you want to study what delta-subunit tonic GABA-A current actually does in a circuit, gaboxadol is effectively the only clean pharmacological lever. That’s a real niche, and it’s gotten more interesting since the brexanolone and zuranolone data validated the delta-subunit angle for neurosteroid-sensitive states. Labs working on PMDD biology, alcohol use disorder, stress-related changes in inhibitory tone, or sleep architecture at the subunit level are going to want this compound on the shelf.

The evidence picture is decent for a failed drug. Multiple Phase 3 trials ran to completion before the adverse event signal emerged. That means there’s actual human pharmacology data: real EEG effects, real sleep architecture changes, real CNS penetration confirmed by the adverse events themselves. Preclinical literature is solid and multi-lab. The translational signal is real but it points toward a wall therapeutically, which is why the score here isn’t higher overall.

Honestly, if you’re not working on GABA-A subunit biology specifically, this compound probably isn’t your priority. The clinical failure isn’t a reason to ignore it, but it does mean the research community actively using it is a specialist one. For those investigators, it’s close to indispensable. For everyone else, it’s a footnote in GABA pharmacology history with a genuinely interesting mechanism they probably won’t have occasion to use.

Novelty

48

Mechanism promise

68

In-category differentiation

72

Evidence quality

60

Translational signal

45

Research bench value

75

Rationale Gaboxadol failed Phase 3 as a hypnotic due to adverse psychiatric events, but the mechanism is intact and validated; it scores high on differentiation and bench value because no other compound selectively probes extrasynaptic delta-containing GABA-A receptors with the same precision, making it indispensable for labs working on tonic inhibition, neurosteroid sensitivity, or delta-subunit biology specifically.

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

Selective extrasynaptic GABA-A delta-subunit agonist

A 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol agonist selective for extrasynaptic GABA-A receptors containing the delta subunit; investigated as a hypnotic.

Abstract

Gaboxadol (THIP; 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; CAS 64603-91-4; molecular formula C6H8N2O2; molecular weight 140.14) is a selective extrasynaptic GABA-A receptor agonist developed at Lundbeck and Merck through the 1990s and 2000s. Distinct from benzodiazepines and barbiturates by selective binding to GABA-A receptor isoforms containing the delta subunit (alpha4-beta3-delta and alpha6-beta3-delta), which are predominantly extrasynaptic and mediate tonic (continuous, low-amplitude) inhibition rather than the phasic (high-amplitude, transient) inhibition mediated by synaptic alpha1/2/3-beta-gamma2 receptors. The compound is a superagonist at delta-containing receptors (efficacy greater than that of GABA itself). Phase 3 trials in primary insomnia (2007) were halted following adverse psychiatric events including disorientation and hallucinations; development was abandoned. The compound retains research utility as the canonical extrasynaptic delta-GABA-A agonist for academic GABA pharmacology and sleep architecture studies. Plasma half-life is approximately 1.5 to 2 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-255Open 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
Tofisopam

Plain-language summaryIntrigue 56 / 100

Tofisopam (Grandaxin) is an unusual benzodiazepine from EGIS in Hungary, registered in the 1960s. The chemistry is technically a benzodiazepine, but the substitution pattern (a 2,3-fused ring rather than the standard 1,4-fused ring of diazepam and lorazepam) means it does not bind the classic GABA-A benzodiazepine site at all. As a result it produces anxiolysis without sedation, muscle relaxation, cognitive impairment, or dependence. The actual mechanism is not fully worked out, with proposals including phosphodiesterase inhibition and dopaminergic modulation. Approved across Europe and parts of Asia for anxiety and autonomic dysfunction; never approved in the US. Genuinely interesting pharmacologically because it shows that the benzodiazepine scaffold can do more than activate GABA-A. 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

51/100

A structurally distinct non-GABA-A anxiolytic with real probe value and an incompletely mapped mechanism worth investigating

Here’s the thing about tofisopam: it’s not a benzodiazepine in the way that word usually lands. Yes, the diazepine ring is there, but the nitrogen positions are at the 2,3 carbons rather than the 1,4 positions of diazepam or lorazepam, and that single structural difference eliminates binding at the classical benzodiazepine allosteric site on GABA-A receptors entirely. That means no sedation from GABA current potentiation, no muscle relaxation from that pathway, and by most accounts no physical dependence profile that mirrors classical benzos. EGIS Pharmaceuticals in Hungary developed it in the 1960s, and it’s been marketed as Grandaxin in Hungary, France, and several Asian markets for decades under indications that include anxiety, autonomic instability, and post-stress recovery. For a compound this old to still have an incompletely characterized mechanism is either a red flag or a research opportunity depending on how you look at it.

We lean toward opportunity, cautiously. The leading hypotheses for tofisopam’s activity include phosphodiesterase IV (PDE4) inhibition and some form of dopaminergic modulation, possibly both operating in parallel. PDE4 inhibition is not a trivial mechanism: roflumilast got approved for COPD on that axis, and the neuroimmune and cognitive implications of PDE4 in the CNS have attracted serious attention over the last decade. If tofisopam genuinely hits PDE4 with relevant potency in neural tissue, thats a more interesting story than it usually gets credit for. The dopaminergic angle is less characterized but could explain the reported antifatigue and mood-brightening effects that dont fit a pure anxiolytic profile. What we dont have is a clean pharmacological dissection confirming which target drives which effect at clinically relevant concentrations.

The evidence base is the main drag on the score. Tofisopam has human approval, which is real, but the supporting literature is heavily weighted toward Eastern European clinical work from the 1970s through the 1990s, published in journals that dont make modern replication standards easy to verify. There isnt a modern phase 2 or phase 3 RCT benchmarking it against placebo or active comparators with current methodology. The preclinical literature is sparse compared to what you’d want before building a research program around it.

Where tofisopam earns its keep is as a reference tool. If your lab is trying to understand what non-GABAergic, non-serotonergic anxiolysis looks like pharmacologically, it’s essentially the only 2,3-benzodiazepine with a usable human history and commercial availability. That niche is real but narrow. Honestly, it scores where it scores because it’s genuinely interesting as a probe without being important enough in any active research conversation to rank higher. Investigators in autonomic pharmacology or PDE4 neuroimmunology should know it exists.

Novelty

42

Mechanism promise

55

In-category differentiation

60

Evidence quality

40

Translational signal

48

Research bench value

60

Rationale Tofisopam’s 2,3-benzodiazepine scaffold genuinely sidesteps classical GABA-A activity, making it the reference probe for non-sedating, non-dependence-forming anxiolysis via a mechanism that still isn’t fully nailed down; the European approval provides a real human signal, but the evidence base is dominated by older Eastern European literature with limited modern replication, keeping differentiation and bench value from pulling the score higher.

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

2,3-benzodiazepine atypical anxiolytic

A 2,3-benzodiazepine without classical GABA-A activity; a non-sedating anxiolytic marketed in Europe.

Abstract

Tofisopam (1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine; CAS 22345-47-7; molecular formula C22H26N2O4; molecular weight 382.46) is a 2,3-benzodiazepine developed at EGIS (Hungary) in the 1960s and approved in Hungary, France, and other European and Asian markets under the trade name Grandaxin. Distinct from the 1,4-benzodiazepine class (diazepam, lorazepam, etc.) by the position of the nitrogens in the diazepine ring: the 2,3 isomer does not bind the classical benzodiazepine site on GABA-A receptors and lacks the GABA-A-mediated sedation, anxiolysis, and dependence of conventional benzodiazepines. The mechanism is incompletely characterized; possibilities include phosphodiesterase IV inhibition and modulation of dopaminergic signaling. Plasma half-life is approximately 6 to 8 hours; metabolism is hepatic. Approved indications in markets where registered include anxiety disorders, autonomic instability, and post-stress recovery; off-label use in fatigue and reactive depression. Not approved in the US. Used as a reference 2,3-benzodiazepine.

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-254Open 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
Propranolol

Plain-language summaryIntrigue 73 / 100

Propranolol (Inderal) is the first commercially successful beta-blocker, developed by James Black at ICI and approved by the FDA in 1967. Black’s work on it earned him the Nobel Prize and reshaped cardiovascular medicine. It blocks both subtypes of beta-adrenergic receptor, dampening the heart’s response to adrenaline as well as the bronchial and metabolic effects. Beyond its many cardiovascular uses, it has a substantial second life in psychiatry and neurology: it is the standard prescription for performance anxiety (one or two tablets before public speaking blunts the heart-pounding and tremor without affecting cognition), is first-line for migraine prevention, and has been studied for trauma memory reconsolidation in PTSD. Lipophilic enough to cross into the brain, which contributes to both its therapeutic and side effects. 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 workhorse

41/100

Historical cornerstone with almost no remaining research novelty; valuable as a canonical non-selective beta-blocker probe

Look, propranolol is one of the most consequential drugs in the history of pharmacology. James Black’s Nobel Prize was built partly on it. And yet, as a research target in 2026, it’s almost entirely spent. That’s the tension the score reflects, and it’s not a close call.

The cardiovascular evidence base is airtight. Hypertension, angina, atrial fibrillation, migraine prophylaxis, essential tremor — six approved indications and decades of replicated RCTs sitting behind each of them. The pharmacokinetics have been characterized exhaustively: non-selective beta-1 and beta-2 blockade, 3-to-6 hour half-life, high lipophilicity giving CNS penetration that hydrophilic competitors like atenolol and nadolol simply lack. Those properties earned it permanent status as the reference non-selective beta-blocker. That reference-compound identity is essentially its only remaining research value — real, but narrow.

The most interesting live research angle is the PTSD memory reconsolidation work, and we want to be honest about what that actually is. The mechanistic logic is genuinely clever: noradrenergic signaling in the basolateral amygdala is required for fear memory reconsolidation, so blocking beta-adrenergic receptors during a deliberate recall event should attenuate reconsolidation and weaken the traumatic memory. Pitman’s Harvard MGH group published the original proof-of-concept in 2002. Alain Brunet’s Montreal lab has been the most persistent investigator, including a 2018 randomized trial in PTSD patients showing meaningful symptom reduction. The signal is real. But the 2019 Cochrane review found the evidence base insufficient, effect sizes across studies are modest, and its been 24 years since the founding paper. Calling this novel would be a stretch.

The novelty problem is fundamental. Beta-adrenergic blockade has been understood mechanistically since the 1960s. No new chemistry, no new mechanisms, no structural innovations. For reconsolidation paradigms specifically, metoprolol covers most of the same ground, and timolol is another option with similar CNS access. Propranolol has first-mover advantage in this niche and a denser associated literature, but its not uniquely irreplaceable in most bench designs.

What we like: the translational track record is definitive, and for performance anxiety studies, adrenergic probe work, or reconsolidation paradigms, its the right tool and the right reference. What we don’t like: the mechanism is fully characterized, the novelty is gone, and the questions propranolol can uniquely answer are getting fewer every year. A serious investigator building a new research program around propranolol in 2026 would need a very specific reason. This is a historical cornerstone, not a frontier compound.

Novelty

10

Mechanism promise

20

In-category differentiation

30

Evidence quality

80

Translational signal

80

Research bench value

50

Rationale Propranolol scores extremely low on novelty and mechanism — it’s a 1967 drug with single-receptor, fully-characterized pharmacology and no new chemistry — but pulls evidence and translational scores high owing to its approved-drug status across six indications and 60 years of clinical use; the PTSD memory reconsolidation angle is the most interesting current research use case, but Pitman’s foundational work is 24 years old and replication remains mixed, preventing a meaningful novelty rescue.

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

Non-selective beta-adrenergic antagonist

A non-selective beta-adrenergic antagonist; the first beta-blocker, repurposed for performance anxiety and migraine prophylaxis.

Abstract

Propranolol (1-(naphthalen-1-yloxy)-3-(propan-2-ylamino)propan-2-ol; CAS 525-66-6; molecular formula C16H21NO2; molecular weight 259.34) is a non-selective beta-adrenergic antagonist developed by James Black at ICI and approved by the FDA in 1967 under the trade name Inderal. The compound is the first commercially successful beta-blocker, foundational to modern cardiovascular pharmacology. Beta-1 affinity is approximately equal to beta-2 affinity (non-selective). Plasma half-life is 3 to 6 hours; the lipophilic structure produces high CNS penetration, distinguishing propranolol from hydrophilic beta-blockers (atenolol, nadolol) for indications requiring central effect. Approved indications include hypertension, angina, atrial fibrillation, migraine prophylaxis, essential tremor, and hypertrophic cardiomyopathy. Off-label use is extensive: performance anxiety (most common psychiatric indication), PTSD memory reconsolidation, akathisia, hyperthyroid tachycardia. The 5-HT receptor partial agonism (weak) was a former curiosity but is not clinically meaningful at standard doses. Used as the canonical non-selective beta-blocker reference compound.

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-256Open 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
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
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
YK-11

Plain-language summaryIntrigue 50 / 100

YK-11 is an unusual SARM developed in Japan that, unlike most SARMs, retains a steroid-like backbone (modified androstane). In cell-culture studies it acts as a partial androgen receptor agonist and was reported to induce follistatin, a protein that blocks myostatin (the muscle-growth brake). The combination, in theory, would drive both androgen-receptor and myostatin-pathway muscle growth. The follistatin data come almost entirely from a single Japanese laboratory and have not been independently replicated in vivo. There are no human trials, no pharmacokinetic data, and persistent reports of liver-enzyme elevation in users. Treat the muscle-growth claims as hypothesis, not established fact. 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.

SARM with myostatin-related activity

A non-steroidal SARM with reported follistatin-inducing and myostatin-modulating activity beyond AR agonism.

Abstract

YK-11 (17-alpha,20E-(((((4-methoxyphenyl)sulfonyl)methylene)-bisoxy))-17-beta-(methoxycarbonyl)methyl-androst-1,4-dien-3-one; molecular formula C25H34O6; molecular weight 430.54) is a structurally novel SARM developed in Japan and described initially by the Yale-Kanno group at Toho University. Distinct from aryl propionamide SARMs by retaining a steroidal scaffold (modified androstane); the compound was reported as a tissue-selective AR partial agonist with concurrent induction of follistatin in C2C12 myoblast cultures, theoretically producing additive muscle hypertrophy through myostatin pathway inhibition. The follistatin-inducing claim is supported by a single research group and has not been independently replicated. No clinical trials. The compound is widely used recreationally as a high-potency SARM-class agent. Plasma half-life and pharmacokinetic data are sparse.

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-267Open 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
S-23

Plain-language summaryIntrigue 52 / 100

S-23 is a SARM developed by GTx that stands out as a full androgen receptor agonist (rather than the partial agonism of most SARMs), producing the strongest hormonal suppression in the class. Preclinical studies showed reversible suppression of sperm production in male rodents, and S-23 was investigated as a candidate component of a male hormonal contraceptive when paired with a progestin. It also shows the typical SARM profile of muscle and bone activity with reduced prostate effect. No human clinical trials have been published, so almost everything known about safety in people comes from anecdote. WADA-banned. 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 compoundSingle-lab provenance

37/100

A preclinical-only full AR agonist SARM with a genuinely niche contraceptive angle but zero human signal

Look, S-23 is an interesting edge case in the SARM landscape, and we want to be precise about why it’s interesting before we explain why it doesn’t score very high. Most SARMs are partial AR agonists by design; partial agonism is the whole trick that lets them claim tissue selectivity without full androgenic load. S-23 breaks from that pattern. It’s a full agonist at the androgen receptor, which means its HPG suppression is substantially more aggressive than anything else in the class. That distinction matters. Researchers studying male hormonal contraception have been circling the idea of a combined SARM-plus-progestin regimen for over a decade, and S-23 became one of the more studied candidates for that specific use case in rodent models precisely because of how reliably it shuts down spermatogenesis.

The problem is the evidence base is almost entirely preclinical, and a large fraction of what exists originated from the GTx research pipeline or closely affiliated academic groups. Replication outside that orbit is limited. There are no published human clinical trials at this writing, which isn’t automatically disqualifying for a research compound, but it does mean the translational signal is essentially absent. You have a plausible mechanism and a real rodent phenotype. What you don’t have is any confirmation that the rodent pharmacology translates to human HPG dynamics in the way the contraceptive story requires.

The bench utility is real but narrow. If you’re running an androgen receptor biology program, S-23 is a legitimate probe for studying full vs. partial agonism at the AR, and the HPG suppression phenotype gives you a clean endpoint to work with in small animal models. Thats a specific utility and we don’t want to dismiss it. But it’s not a broadly indispensable tool the way rapamycin is for mTOR work. It’s a specialist instrument for a specific set of questions.

What we dont like: the recreational use context creates a messy signal-to-noise problem for serious investigators, the recovery profile post-exposure is the worst in class, and the compound sits in a regulatory gray zone that complicates institutional research approvals. The SARM class is also crowded enough that the full-agonist angle, while genuinely differentiating, hasn’t attracted the multi-lab attention it would need to build a real evidence stack. Honestly, S-23 would be a more compelling library entry if even one well-designed Phase 1 contraception trial had been completed. As it stands, it’s a preclinical compound with an interesting story and a thin dossier.

Novelty

38

Mechanism promise

42

In-category differentiation

50

Evidence quality

22

Translational signal

18

Research bench value

45

Rationale S-23 earns modest differentiation within the SARM class by being the only full AR agonist with a documented contraceptive research track record in rodents, but the complete absence of human clinical data and the likely narrow origination of most preclinical work (GTx-adjacent) keeps evidence and translational scores very low. The SARM class itself is mature enough that novelty is constrained even with the HPG-suppression angle.

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

Selective androgen receptor modulator

A non-steroidal SARM with reported male contraceptive activity in preclinical studies; full agonist at the AR with strong HPG suppression.

Abstract

S-23 (CAS 1010396-29-8; molecular formula C18H13ClF4N2O3; molecular weight 416.76) is a non-steroidal SARM developed by GTx. Distinct among SARMs as a full AR agonist (rather than a partial agonist), producing more pronounced HPG axis suppression alongside strong anabolic activity. Preclinical studies in male rodents demonstrated reversible spermatogenesis suppression; the compound was investigated as a candidate for male hormonal contraception via combined progestin and SARM regimen. Tissue-selective effects: full agonism in muscle and bone with reduced prostate activity relative to testosterone. The strong HPG suppression makes S-23 the most stringent SARM in terms of post-cycle endocrine recovery. No human clinical trials at this writing. Used recreationally despite the suppressive profile.

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-268Open 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
LGD-3303

Plain-language summaryIntrigue 42 / 100

LGD-3303 is a less-well-known SARM from Ligand Pharmaceuticals, developed as a candidate for osteoporosis. In ovariectomized rat models (the standard postmenopausal-bone preclinical model) it produced bone anabolic effects comparable to or exceeding raloxifene, with relatively favorable bone-versus-muscle selectivity. Phase 1 human studies were conducted but the compound did not advance further, and full clinical results were never published. It is occasionally encountered as a research chemical but is much less common than ostarine or ligandrol. Limited human data and an inactive development program limit clinical relevance. 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

32/100

Bone-selective SARM with a stalled development record and thin independent evidence base

Look, LGD-3303 deserves a fair read before you dismiss it, but that fair read lands it pretty low on the priority list. It’s a non-steroidal SARM with a genuinely interesting tissue selectivity profile: preclinical data in ovariectomized rats showed bone anabolic activity on par with or exceeding raloxifene, while prostate-sparing effects were better than what you’d expect from a compound this anabolically active. That tissue dissociation story is the most interesting thing LGD-3303 has going for it. Most SARMs optimize for muscle. This one was explicitly engineered for bone. Thats a real, if narrow, research angle.

Here’s the thing though. Ligand ran a Phase 1 and then stopped. The compound never moved to Phase 2, and there’s no public explanation for why. That’s a ceiling, not a floor. It means the entire human-relevant evidence base is a pharmacokinetics read from a Phase 1 trial that wasn’t followed up. We’re not saying the compound failed on efficacy in humans, we’re saying we simply dont know, and the developer apparently decided the answer wasn’t worth finding out. That’s a worse position than compounds with failed Phase 2s, because at least failed Phase 2s tell you something.

The preclinical literature itself is fine but narrow. Rodent osteoporosis models are a legitimate research tool, and the OVX rat work for LGD-3303 is competent. But the independent replication is basically absent. This is a Ligand-generated compound with a Ligand-generated evidence base. The SARM class broadly has had the same problem: most of the interesting early preclinical work comes from the groups that developed the compounds. Multi-lab independent confirmation for LGD-3303 specifically is sparse.

Where we think LGD-3303 retains real, if limited, utility is as a bench-level probe for investigators studying AR conformation and tissue-selective signaling in bone biology. Its selectivity profile is genuinely distinct from RAD-140 or LGD-4033, and if your research question is about how AR agonist conformation drives tissue preference, having LGD-3303 in the panel alongside ostarine and RAD-140 gives you a data point you can’t get otherwise. The 24-hour plasma half-life is also convenient for rodent dosing protocols. That’s not nothing.

But honestly, if you’re not specifically interrogating bone-selective AR pharmacology, theres no compelling reason to put LGD-3303 on your bench over better-evidenced SARMs. The novelty is modest, the human signal is almost absent, and the development history doesn’t inspire confidence. We score it where the evidence puts it: a niche probe with a specific but narrow use case, not a compound to prioritize in a general research program.

Novelty

28

Mechanism promise

38

In-category differentiation

35

Evidence quality

28

Translational signal

22

Research bench value

38

Rationale LGD-3303 scores low primarily because Phase 1 completion without Phase 2 advancement is a genuine negative translational signal, and the evidence base is almost entirely from Ligand’s own development program. The bone-over-muscle selectivity is a real and mechanistically interesting differentiator within the SARM class, but it isn’t compelling enough to offset thin replication and a dead development program.

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

Selective androgen receptor modulator

A non-steroidal SARM developed by Ligand Pharmaceuticals for osteoporosis; less studied than ligandrol.

Abstract

LGD-3303 (9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo[3,2-f]quinolin-7(6H)-one; molecular formula C16H14ClF3N2O; molecular weight 342.74) is a non-steroidal SARM developed by Ligand Pharmaceuticals as a candidate for osteoporosis. Preclinical studies in ovariectomized rats demonstrated strong bone anabolic activity comparable to or exceeding raloxifene at appropriate doses, with reduced prostate effects. Tissue selectivity profile favors bone over muscle within the SARM class. Phase 1 human studies were conducted but the compound did not advance to phase 2. The compound retains research utility for bone-focused SARM pharmacology and is occasionally used recreationally. 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-269Open 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 … 63 64 65 66 67 … 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.