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Author: kodiac

Liothyronine (T3)

Our opinion on this compoundEstablished workhorse

46/100

Canonical active thyroid hormone with strong clinical evidence but minimal research frontier value

Look, this is the canonical active thyroid hormone. Liothyronine has been around since before most researchers in this field were born, it binds TR-alpha and TR-beta with roughly 4x the affinity of T4, and the mechanism, genomic transcription of metabolic target genes through nuclear hormone receptor activation, was worked out thoroughly decades ago. That’s not a knock on the compound. It’s a knock on it as a research target in 2026.

What we like about T3 in the context of the library is that its pharmacokinetics make it a genuinely useful probe. The 2.5-day half-life versus T4’s 7-day half-life means you can actually titrate thyroid hormone state in a model organism or cell system with reasonable temporal precision. That has real bench utility for anyone studying metabolic gene regulation, cardiac hypertrophy models, or thyroid receptor biology. Its role as the reference standard for TR assays is legitimate and worth acknowledging.

Here’s the thing though: the interesting thyroid hormone pharmacology right now is happening at selective TR-beta agonists. Resmetirom just got FDA approval for MASH and that story, receptor-subtype selectivity to preserve metabolic benefit while shedding cardiac risk, is where the research conversation is. T3 hits both TR-alpha and TR-beta, which means it carries the full cardiac liability and doesn’t let you cleanly dissect receptor subtype contributions. As a research tool for that question, its nonselective profile is actually a limitation.

The STAR*D T3 augmentation data is real and worth knowing about. Adding T3 25 to 50 mcg to a partially-responding antidepressant did produce a 24.7% remission rate in the augmentation arm of that massive NCI-sponsored trial, which is a meaningful signal. But thats not new territory. The depression augmentation mechanism isn’t well-understood (thyroid hormone’s relationship to neurotransmitter sensitivity, particularly 5-HT1A and beta-adrenergic systems, remains speculative), and nobody is running novel T3 depression trials because the clinical question was largely answered.

We’d put T3 in the library as a reference compound and a functional tool for groups studying thyroid axis biology or receptor pharmacology. For someone building a metabolic research program or doing GH axis work where thyroid hormone status matters as a cofactor, having T3 on hand is just practical. But if you’re looking for something with genuine investigational upside in 2026, the TR-beta selective program is where you’d spend your reading time, not on T3 itself. The evidence is mature. The mechanism is settled. The frontier has moved on.

Novelty

18

Mechanism promise

28

In-category differentiation

38

Evidence quality

75

Translational signal

75

Research bench value

65

Rationale T3 scores well on evidence quality and translational signal as an approved drug with decades of clinical use and STAR*D-validated depression augmentation, but those strengths reflect maturity, not novelty; the compound’s low novelty, well-characterized nuclear receptor mechanism, and limited differentiation relative to emerging TR-beta selective agonists (resmetirom, MGL-3196) drag the overall to the mid-40s despite its reference-standard bench utility.

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

Active thyroid hormone (T3)

The active thyroid hormone triiodothyronine; faster-acting and more potent than levothyroxine, used in hypothyroidism, depression augmentation, and metabolic research.

Abstract

Liothyronine (3,3′,5-triiodo-L-thyronine, T3; CAS 6893-02-3; molecular formula C15H12I3NO4; molecular weight 650.97) is the active thyroid hormone, marketed as Cytomel for hypothyroidism. The compound binds thyroid hormone receptors (TR-alpha, TR-beta) with approximately 4-fold higher affinity than thyroxine (T4) and produces direct genomic effects on metabolic gene transcription without the conversion delay required for T4. Plasma half-life is 2.5 days, much shorter than T4’s 7-day half-life, producing more variable plasma levels but faster onset and offset. Approved for hypothyroidism (alternative or adjunct to levothyroxine), myxedema coma (intravenous), and as a thyroid suppression test. Off-label use in major depressive disorder augmentation (the STAR*D trial-supported strategy of T3 25 to 50 mcg added to a partially-responding antidepressant), fat loss, and bodybuilding cutting cycles. The cardiac risk is the principal limitation: T3 directly increases myocardial oxygen demand, producing tachycardia, atrial fibrillation, and angina at supratherapeutic doses. Used as the canonical T3 reference compound.

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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
Alpha-Ketoglutarate (AKG)

Plain-language summaryIntrigue 65 / 100

Alpha-ketoglutarate (AKG) is a TCA cycle intermediate that has shown lifespan extension in mouse studies. Calcium AKG (Ca-AKG) is sold as a longevity supplement, popularized by Rejuvant. 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

44/100

Old metabolite with a genuinely interesting epigenetic aging angle, but thin human evidence and COI-clouded pilot data keep it mid-tier

Look, AKG has been sitting in the TCA cycle since the first organisms figured out oxidative metabolism. Calling it novel is a stretch. But there’s a specific modern angle that deserves a serious look: AKG is a required co-substrate for the 2-oxoglutarate-dependent dioxygenase (2-OGDD) superfamily, which includes TET enzymes driving DNA demethylation, JmjC-domain histone demethylases, and prolyl hydroxylases feeding into HIF pathway regulation. When plasma and tissue AKG levels fall with age, which they do, you’re potentially starving a set of enzymes that maintain epigenetic fidelity. That’s a real mechanistic hypothesis, not just “it’s in the Krebs cycle so it must be good.”

The animal data is what put Ca-AKG on the map for longevity researchers. The 2020 work (Shahmirzadi et al., Cell Metabolism) showed Ca-AKG supplementation at 2 percent chow concentration extended healthspan and lifespan in mice, with reduced senescence markers and attenuated inflammaging signals. The C. elegans results are older and show up to 50 percent lifespan extension, though worm data translates poorly. The mouse work is from a real lab with real methodology, but it’s essentially one study from one group at this point.

The human pilot is where things get complicated. Tian et al. 2022 (Aging journal, n=42, open-label) reported roughly 8 years of epigenetic age reduction using Horvath-type methylation clocks after Rejuvant supplementation. What we like: it’s actual human data with a pre-specified methylation endpoint, which is rare in this space. What we dont like: the study is from the Rejuvant commercial team, its open-label with no placebo arm, and epigenetic clocks as primary endpoints remain contested even among clock developers. Replicated, blinded data from independent groups simply doesnt exist yet.

As a bench tool, AKG has real utility for investigators studying 2-OGDD biology or aging-related epigenetic drift. If you’re running a research program on TET enzyme activity, substrate availability experiments are straightforward and informative. The compound is easy to source, stable, and inexpensive. That’s worth something, even if it’s not a sophisticated probe.

We think the 2-OGDD epigenetic aging story is the most interesting thing going on with this compound, and it’s underexplored relative to the NAD+/sirtuin and mTOR spaces that absorb most longevity research attention. But the honest assessment is that the human evidence is one small, conflict-laden pilot, and the mouse mechanism is incompletely worked out. This is a compound worth watching, not one to prioritize. If independent groups replicate the methylation clock findings in a blinded design, the score goes up meaningfully.

Novelty

38

Mechanism promise

58

In-category differentiation

45

Evidence quality

37

Translational signal

35

Research bench value

45

Rationale AKG would normally sit under the foundational-metabolite cap, but the 2-oxoglutarate-dependent dioxygenase story for epigenetic aging qualifies as a novel indication with real (if preliminary) human signal, lifting the cap exemption. Scores land in the low-40s because the mechanism is compelling but the evidence base is thin and largely consortium-sourced.

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

TCA cycle intermediate / 2-oxoglutarate

A TCA cycle intermediate sold as calcium alpha-ketoglutarate (Ca-AKG) for longevity applications based on extension of lifespan in mice and worms.

Abstract

Alpha-Ketoglutarate (AKG, 2-oxoglutarate; CAS 328-50-7; molecular formula C5H6O5; molecular weight 146.10) is a tricarboxylic acid cycle intermediate that declines with age in plasma and tissues. The compound is a substrate for the 2-oxoglutarate-dependent dioxygenase family of enzymes (including DNA and histone demethylases, prolyl hydroxylases, and TET enzymes), placing it at a hub of cellular regulation. AKG supplementation extends lifespan in C. elegans (up to 50 percent) and in mice when given as the calcium salt at 2 percent in chow. The mechanism in mice is incompletely characterized but appears to involve reduced cellular senescence, improved metabolic flexibility, and reduced inflammaging markers. Sold as calcium alpha-ketoglutarate (Ca-AKG, Rejuvant) for supplemental use. Doses are typically 500 to 2000 mg per day.

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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
Human Chorionic Gonadotropin (HCG)

Glycoprotein hormone (LH analog; placental origin)

Human chorionic gonadotropin; a placental glycoprotein hormone that activates the LH receptor; used in IVF, hypogonadism, and HPG axis recovery.

Abstract

Human chorionic gonadotropin (hCG; CAS 9002-61-3; alpha subunit and unique beta subunit; total molecular weight approximately 36800 Da) is a placental glycoprotein hormone composed of an alpha subunit (shared with LH, FSH, and TSH) and a unique beta subunit. The compound is the principal hormone of pregnancy, produced by syncytiotrophoblasts of the implanting embryo and detected as the basis for pregnancy tests. Pharmacologically, hCG acts as an LH receptor agonist with a substantially longer half-life than endogenous LH (approximately 36 hours versus 30 minutes), making it useful as a pharmacological tool to stimulate Leydig cell testosterone production in males or to trigger ovulation in IVF protocols. Approved indications: male hypogonadotropic hypogonadism (testosterone restoration with preservation of fertility), cryptorchidism, and as ovulation trigger in IVF (single 5000 to 10000 IU injection). Off-label use in TRT users to restore testicular function or as part of post-cycle therapy after AAS or SARM use. Plasma half-life of urinary-derived (Pregnyl, Novarel) versus recombinant (Ovidrel) forms are similar; both work clinically. Used as the canonical LH receptor agonist in HPG axis research.

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May 9, 2026
Thyrotropin-Releasing Hormone (TRH)

Hypothalamic tripeptide (thyrotropin-releasing hormone)

A hypothalamic tripeptide that triggers pituitary TSH release; used as a pharmacological probe for pituitary function and investigated for cognitive enhancement.

Abstract

TRH (thyrotropin-releasing hormone; pyroglutamyl-histidyl-prolinamide; CAS 24305-27-9; molecular formula C16H22N6O4; molecular weight 362.39) is a hypothalamic tripeptide that activates pituitary TRH receptors to trigger TSH release. Discovered independently by Schally and Guillemin in the late 1960s (Nobel Prize 1977). The compound is the smallest peptide hormone of the hypothalamic-pituitary axis. Pharmacologically, exogenous TRH has been used as a clinical probe of pituitary thyrotroph function (the TRH stimulation test, now largely supplanted by sensitive TSH assays). Beyond TSH release, TRH receptors are distributed throughout the CNS and TRH has direct effects on arousal, mood, and cognitive function; clinical trials in depression, ALS, and spinocerebellar ataxia have been mixed. Plasma half-life is approximately 5 minutes, severely limiting clinical use; analog development has produced taltirelin (approved in Japan for spinocerebellar degeneration) and other TRH receptor agonists with extended pharmacokinetics. Used as the canonical hypothalamic peptide for pituitary axis research.

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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
Levothyroxine (T4)

Our opinion on this compoundEstablished workhorse

41/100

The canonical hypothyroidism workhorse, mature beyond argument, with near-zero research novelty

Look, levothyroxine is the most prescribed drug in the United States. That sentence alone should tell you everything you need to know about where it sits on the research-interest spectrum. When something is this thoroughly characterized, this embedded in standard-of-care medicine, the frontier questions arent really about the compound anymore.

The mechanism is completely understood. T4 is a prohormone. Deiodinases D1 and D2 convert it to active T3 in target tissues. T3 binds thyroid hormone receptors TR-alpha and TR-beta, which are nuclear receptors driving gene transcription programs governing metabolism, thermogenesis, cardiac function, neurological development, and protein synthesis. We’ve known all of this for a long time. There’s no elegant new biology here, no dual-target surprise, no mechanism that reframes a whole field. Its a single-pathway prohormone doing exactly what a prohormone does.

What we do credit it for: as a reference compound for T4-biology work, its the canonical standard. Deiodinase enzyme assays, tissue-specific T4-to-T3 conversion studies, thyroid hormone receptor binding experiments — if you’re running that kind of work, levothyroxine is your T4. That earns it a real bench value score, not a heroic one. You wouldnt study deiodinase biology without it, but you wouldnt build a research program around it either.

The evidence quality and translational signal scores are genuinely high because the clinical record is enormous. Multiple decades of randomized data, regulatory approval in 1955, replicated across every conceivable patient population. The Synthroid vs. generic bioequivalence debates of the late 1990s and the absorption interaction literature are among the more practically useful pieces of pharmacokinetic research in all of thyroid medicine. None of that is exciting from a frontier standpoint; all of it is useful if youre doing clinical or PK work in the thyroid space.

Honestly, the interesting research questions adjacent to T4 right now are elsewhere: the debate over T4-only vs. T4/T3 combination therapy and what it means for deiodinase polymorphisms; the tissue-specific hypothesis about local D2 activity in brain vs. periphery; the emerging pharmacogenomics around DIO2 variants. Those questions involve T4, but theyre not really questions about T4. Levothyroxine the compound is the solved variable; the biology around its conversion and receptor selectivity is where any remaining signal lives. We score it where the rubric forces it: high evidence, low novelty, net 41.

Novelty

8

Mechanism promise

16

In-category differentiation

20

Evidence quality

90

Translational signal

88

Research bench value

50

Rationale Levothyroxine scores extremely high on evidence and translational signal because it is, simply, one of the most validated drugs in human medicine — but novelty, mechanism interest, and differentiation are all basement-tier for the same reason: theres nothing left to discover about T4 replacement that hasn’t been settled for decades. The overall of 41 reflects this tension: outstanding clinical data dragging up a compound that offers essentially nothing to a research frontier investigator.

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

Thyroid prohormone (T4)

Synthetic thyroxine; the standard hypothyroidism treatment and the most prescribed drug in the United States.

Abstract

Levothyroxine (3,3′,5,5′-tetraiodo-L-thyronine, T4; CAS 51-48-9; molecular formula C15H11I4NO4; molecular weight 776.87) is synthetic L-thyroxine, the principal thyroid hormone produced by the thyroid gland. Approved by the FDA from 1955 (multiple manufacturers; brands include Synthroid, Levoxyl, Tirosint). The compound is a prohormone: T4 is converted by deiodinases (D1, D2) to active T3 in target tissues. The prohormone strategy provides smoother plasma levels than direct T3 administration, reflecting the long T4 half-life (approximately 7 days). Approved indications include primary, secondary, and tertiary hypothyroidism; thyroid cancer suppression therapy; goiter; and myxedema coma. Levothyroxine is the most prescribed drug in the United States by prescription count. Plasma half-life is approximately 7 days; absorption is impaired by food, calcium, iron, and proton pump inhibitors, requiring administration on an empty stomach with at least 4-hour spacing from interfering substances. Used as the canonical T4 reference compound.

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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
Tiratricol (TRIAC)

Our opinion on this compoundNiche research probe

41/100

A historical TR-beta probe now outclassed by resmetirom; retains niche value in RTH syndrome research

Look, TRIAC is one of those compounds that used to be the most interesting thing in its zip code and simply isn’t anymore. It’s a natural T3 metabolite, formed by deamination and oxidative decarboxylation of T3, and it retains thyroid receptor activity with a modest TR-beta preference somewhere around 2 to 4-fold over TR-alpha. That selectivity ratio was genuinely exciting in the 1980s and early 1990s when TR-beta-selective thyromimetics were a hot theoretical concept. It’s a lot less exciting now that resmetirom (Rezdiffra) has been FDA-approved for MASH with a vastly superior selectivity profile and a phase 3 dataset behind it.

The TR-beta biology here is real. TR-beta drives effects in the pituitary and liver; TR-alpha drives the cardiac and skeletal effects you don’t want. TRIAC’s selectivity is enough to produce the pituitary suppression you need in resistance to thyroid hormone syndrome (Refetoff syndrome) without the same degree of tachycardia and bone turnover you’d get from equivalent T3 exposure. That’s why it’s approved in France, Mexico, and a handful of other markets for RTH. It’s a legitimate approved compound with a real mechanism solving a real problem in a real patient population. We don’t want to dismiss that.

What we do want to flag is that the population is rare, the clinical trials were small, and the broader thyromimetic literature has moved decisively past TRIAC in terms of selectivity and precision. Sobetirome, VK2809, and now resmetirom all do the TR-beta job better. The fat loss angle, which drove a lot of the underground use, produced enough serious thyrotoxic events at supratherapeutic doses to prompt FDA enforcement actions against supplement products containing it. Thats not a research dead end exactly, but it is a credibility problem for any investigator trying to study TRIAC as a metabolic tool in 2025.

Where TRIAC still earns its place in a serious research library is as a reference thyromimetic. If you’re doing TR-beta selectivity work, you need a physiologically relevant natural metabolite as your comparator. TRIAC fills that role. It has decades of receptor-binding data, a well-characterized PK profile (roughly 7-hour half-life, shorter than T4, longer than T3), and the kind of historical dataset that lets you anchor new results against a known standard. The bench utility is real but bounded. You’re reaching for TRIAC when you need that physiological reference, not when you’re trying to advance the field.

Honestly, the score of 41 reflects exactly this situation: a compound that mattered, still has a defined niche, but isn’t where a serious investigator puts their next research dollar unless RTH syndrome or TR-beta reference biology is the specific program. Good tool. Not a frontier compound.

Novelty

28

Mechanism promise

45

In-category differentiation

30

Evidence quality

48

Translational signal

50

Research bench value

60

Rationale TRIAC scores low on novelty and differentiation because it’s a 1960s-era natural metabolite that has been materially superseded by far more selective thyromimetics; its bench value is the score’s floor, since it remains a physiologically relevant TR-beta reference compound and the only orally approved option for Refetoff syndrome in some jurisdictions.

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

T3 metabolite (3,3′,5-triiodothyroacetic acid)

A naturally occurring T3 metabolite with thyroid-receptor activity; used in resistance to thyroid hormone syndrome and (off-label) for fat loss.

Abstract

Tiratricol (TRIAC, 3,3′,5-triiodothyroacetic acid; CAS 51-24-1; molecular formula C14H9I3O4; molecular weight 621.93) is a natural T3 metabolite formed by deamination and oxidative decarboxylation of T3. The compound retains thyroid hormone receptor activity with TR-beta selectivity (approximately 2- to 4-fold over TR-alpha). Approved in France, Mexico, and other markets for resistance to thyroid hormone syndrome (Refetoff syndrome), where the TR-beta selectivity allows TR-beta target tissue (pituitary, liver) effects without the cardiac TR-alpha hyperthyroid effects. Off-label use in obesity and as an athletic fat-loss compound has been documented; the FDA has issued warnings against unapproved supplement products containing tiratricol owing to severe thyrotoxic adverse events at supratherapeutic doses. Plasma half-life is approximately 7 hours, shorter than T4 but longer than T3. Used as a reference TR-beta-selective thyromimetic in research.

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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
Anavex 2-73 (Blarcamesine)

Our opinion on this compoundNovel, promising

60/100

Multi-target sigma-1/muscarinic agonist with genuine Phase 3 Rett syndrome signal and real probe utility in neurodegeneration

Yeah, so blarcamesine isn’t the flashiest thing on the shelf, but it’s doing something that a lot of sigma-1 programs have talked about without actually delivering: it has real clinical confirmation. The EXCELLENCE Phase 3 trial in Rett syndrome reported positive results in 2024, which matters because Rett is a brutal, high-unmet-need condition and the CNS literature is littered with Phase 2 wins that collapse in Phase 3. That it held is worth noting.

The mechanism is where we spend most of our thinking. Sigma-1 receptor is a chaperone protein sitting at the ER-mitochondria interface, involved in calcium signaling, proteostasis, and ER stress modulation. It’s not a classical receptor in the GPCR sense, which makes the pharmacology more complicated and more interesting. Blarcamesine’s sigma-1 affinity sits around 860 nM, which is weaker than cutamesine but still functionally meaningful. What sets it apart is the additional muscarinic M1/M2 activity. Cholinergic deficits are central to Alzheimer’s and Parkinson’s dementia pathology, so hitting both sigma-1 chaperone biology and muscarinic tone simultaneously is a real multi-target rationale, not a coincidence of dirty pharmacology. We like that about it.

The Phase 2 data in Alzheimer’s disease and Parkinson’s disease dementia showed dose-dependent improvements on some cognitive endpoints. Honest take: the AD Phase 2 results were encouraging but not spectacular, and the trial designs had limitations. The Rett syndrome Phase 3 is the strongest evidence pillar right now. That’s a rare disease context with small N, so extrapolating broadly requires caution, but the signal is real and replicated within the program.

As a bench tool, blarcamesine has genuine value for investigators working sigma-1 neuropharmacology or probing ER stress pathways in neurodegeneration models. It’s more pharmacologically interesting than generic sigma-1 ligands precisely because of the muscarinic overlay. If you’re trying to untangle sigma-1-dependent vs. cholinergic contributions to a cellular phenotype, blarcamesine gives you a handle that simpler probes dont. Cutamesine (SA4503) had its Phase 2 stroke trial fail, and fluvoxamine’s sigma-1 activity is inseparable from its SERT pharmacology. Blarcamesine is the most clinically advanced compound with a specific dual sigma-1/muscarinic profile, which gives it differentiation that isnt just theoretical.

What we dont love: the sigma-1 field has been promising a lot for twenty-plus years and the clinical wins have been narrow and indication-specific so far. The Alzheimer’s program needs Phase 3 to answer the real question. But the 2024 Rett result adds legitimacy to the mechanism, and the compound’s probe utility in ER stress and cholinergic neurobiology is solid. For a lab working neurodegeneration or protein homeostasis, this earns a place on the shelf.

Novelty

55

Mechanism promise

65

In-category differentiation

62

Evidence quality

60

Translational signal

62

Research bench value

55

Rationale Blarcamesine’s dual sigma-1/muscarinic profile is meaningfully differentiated from single-target sigma-1 ligands, and the 2024 Phase 3 EXCELLENCE trial positive result in Rett syndrome is the clearest clinical confirmation in its class; however, the Alzheimer’s Phase 2 data is modest and sigma-1 receptor biology, while genuinely interesting, has been pursued since the 1990s, which constrains novelty and mechanism scores.

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

Sigma-1 agonist + muscarinic modulator

A sigma-1 agonist with muscarinic acetylcholine receptor activity; investigated for Alzheimer disease, Parkinson dementia, and Rett syndrome.

Abstract

Anavex 2-73 (blarcamesine, AVN-101; CAS 195615-83-9; molecular formula C16H21NO; molecular weight 243.34) is a multi-target sigma-1 agonist with muscarinic acetylcholine receptor activity, developed by Anavex Life Sciences. Sigma-1 affinity is approximately 860 nM (lower than cutamesine but functionally meaningful); the compound additionally interacts with muscarinic M1 and M2 receptors. Phase 2 trials in Alzheimer disease and Parkinson disease dementia demonstrated dose-dependent improvements in some cognitive endpoints. Phase 3 in Rett syndrome (EXCELLENCE trial) reported positive results in 2024 for select endpoints. Plasma half-life is approximately 14 hours. Used as a multi-target research compound for sigma-1 and muscarinic neuropharmacology.

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May 9, 2026
KPV

Plain-language summaryIntrigue 66 / 100

KPV is a tiny three-amino-acid peptide derived from the C-terminal end of alpha-MSH (the melanocyte-stimulating hormone). It has anti-inflammatory effects, particularly in the gut, and is being studied for inflammatory bowel disease. Stocked in the Kodiac catalog as a research-only powder for laboratory work; not a medicine, not for human consumption.

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

Our opinion on this compoundEstablished, active research

41/100

A 1990s alpha-MSH fragment with real anti-inflammatory preclinical data but thin human evidence and limited novelty

Look, KPV has a genuinely interesting origin story. Back in the early 1990s, Catania and Lipton were doing structure-activity work on alpha-melanocyte stimulating hormone trying to figure out which part of the peptide was responsible for the anti-inflammatory effects versus the parts driving pigmentation, body temperature changes, and feeding behavior. The C-terminal tripeptide, Lys-Pro-Val, retained a lot of the parent hormone’s inflammatory pharmacology without dragging along those other effects. That’s a clean dissection and it’s still the primary reason researchers reach for KPV today.

The mechanism centers on NF-kappa-B attenuation and reduced cytokine output from activated immune cells. NF-kappa-B modulation is not a novel story in 2025; thats a well-trodden pathway with hundreds of compounds claiming to hit it. What makes KPV somewhat more interesting is the melanocortin receptor angle. The specific MCR subtypes responsible for the tripeptide’s anti-inflammatory activity are not fully characterized, which means theres still a real question to answer there. MC1R and MC3R are in the frame, but the binding pharmacology for this three-residue fragment is genuinely incomplete compared to what we know about the full alpha-MSH sequence. That gap is actually useful for bench investigators who want to probe melanocortin-mediated immunomodulation.

The preclinical evidence covers multiple model types: DSS-induced colitis, acute lung injury, contact dermatitis, hepatic ischemia-reperfusion. That breadth is a point in KPV’s favor compared to single-indication peptides. But the literature is noticeably thinner than BPC-157 or TB-500, and neither of those is exactly overflowing with replicated human data. Preliminary clinical work with topical KPV preparations in ulcerative colitis and inflammatory dermatology has been explored, but there’s no FDA-approved IND and human pharmacokinetic data is sparse. We’re firmly in early-human-signal territory, not confirmed efficacy.

Where KPV earns real credit is bench utility. If your research program involves alpha-MSH biology, colitis models, or melanocortin receptor pharmacology, KPV is a legitimate tool. Its short sequence, commercial availability, and defined origin in the alpha-MSH SAR literature make it easier to work with than full-length hormone fragments. The nomenclature confusion around KPV versus KPV-Asn and other fragment lengths is a real sourcing and verification headache; mass spec confirmation of what you’re actually running is essential.

We think KPV is a solid secondary tool for labs already working in MCR or inflammatory peptide biology, but its not a primary research target for most programs. The novelty largely dried up in the 1990s, the human data is thin, and the anti-inflammatory peptide space is crowded. Worth knowing about; not worth centering a program around.

Novelty

35

Mechanism promise

50

In-category differentiation

40

Evidence quality

38

Translational signal

33

Research bench value

52

Rationale KPV scores modestly because most of its structural-activity story was told by Catania and Lipton thirty years ago, and the human evidence base remains early-stage topical work without an approved IND. The partially uncharacterized melanocortin receptor pharmacology and its utility as a probe for dissecting alpha-MSH biology provide genuine but limited upside.

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

Tripeptide C-terminal fragment of alpha-melanocyte stimulating hormone

A 3-amino-acid tripeptide derived from the C-terminus of alpha-MSH, characterized for anti-inflammatory effects in colitis, dermatitis, and hepatic injury models.

Abstract

KPV (sequence Lys-Pro-Val-OH; CAS 67727-97-3; molecular formula C16H30N4O4; molecular weight 342.43) is a synthetic tripeptide corresponding to residues 11-13 of alpha-melanocyte stimulating hormone (alpha-MSH), the C-terminal fragment that retains anti-inflammatory activity in many of the published preclinical models of acute and chronic inflammation. The tripeptide was originally characterized by Catania and Lipton in the early 1990s as part of a structure-activity relationship study of the alpha-MSH inflammatory pharmacology, with the goal of identifying a small fragment that retained the parent hormone’s anti-inflammatory effects without the pigmentation, body temperature, and feeding-behavior effects mediated by the N-terminal portion of the hormone. KPV reproduced the anti-inflammatory effects of alpha-MSH in rodent models of acute lung injury, dextran sulfate sodium-induced colitis, contact dermatitis, and hepatic ischemia-reperfusion injury. The mechanism involves attenuation of NF-kappa-B activation, reduced pro-inflammatory cytokine production by activated immune cells, and modulation of the melanocortin system through receptors that are not yet fully characterized for the tripeptide fragment. There is no FDA-approved IND for KPV in any indication; preliminary clinical work has explored topical KPV preparations for ulcerative colitis and inflammatory dermatologic conditions. The compound is widely used in research-grade work on inflammation and tissue injury. The principal limitations on the strength of the evidence are the relatively small published literature compared to BPC-157 or TB-500 and the limited human pharmacokinetic data.

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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 8, 2026
SS-31

Plain-language summaryIntrigue 88 / 100

SS-31, also called elamipretide, is a four-amino-acid peptide that selectively targets the inner mitochondrial membrane. It binds cardiolipin (a unique mitochondrial lipid) and stabilizes the mitochondrial membrane during stress, with research interest in heart failure, kidney disease, and aging. Stocked in the Kodiac catalog as a research-only powder for laboratory work; not a medicine, not for human consumption.

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

Our opinion on this compoundNovel, promising

63/100

Cardiolipin-targeted mitochondrial probe with real Phase 2/3 clinical data, mixed outcomes, and strong bench utility in mitochondrial disease models

Look, SS-31 is one of those compounds where the mechanism is genuinely beautiful and the clinical story is genuinely complicated. Hazel Szeto’s group at Cornell spent years establishing that cardiolipin, the signature phospholipid of the inner mitochondrial membrane, is a target you can actually modulate with a synthetic tetrapeptide. That insight wasn’t obvious when the SS series was first described. The Dmt substitution over tyrosine in SS-02 wasn’t cosmetic either: it’s what gives SS-31 the stability and binding affinity that makes it useful at all in biological systems, and mass spec distinguishes the two readily enough that adulteration is a tractable quality concern rather than an invisible one.

The mechanistic story is compelling at the bench level. Cardiolipin doesn’t just sit there in the inner membrane looking pretty; it scaffolds the supercomplexes of the electron transport chain, particularly the Complex I/III/IV associations. When you perturb that environment through oxidative stress, the supercomplexes destabilize, electron flow becomes leaky, ROS output increases, and you get the downstream cascade that defines mitochondrial dysfunction in aging and ischemic disease. SS-31 interrupts that cascade upstream, at the lipid level, rather than scavenging ROS after the fact. Thats mechanistically more interesting than antioxidant supplementation and it explains why the compound has stayed in serious investigator hands even as its clinical arc has been uneven.

The clinical translation is where the story gets messier. Stealth BioTherapeutics ran a genuine program: Phase 2 work in cardiac ischemia, heart failure with preserved ejection fraction, Barth syndrome, primary mitochondrial myopathies, and age-related macular degeneration. The AMD program hit a real wall; the FDA issued a complete response letter for geographic atrophy requesting additional data, and that’s a setback that can’t be soft-pedaled. But the Barth syndrome and primary mitochondrial myopathy results are legitimately interesting. Barth is a rare cardiolipin remodeling disorder where elamipretide’s mechanism isn’t just plausible, its almost mechanistically required. Phase 2 functional improvements in that population were meaningful. Primary mitochondrial myopathy data has been more modest but directionally real.

What we like: SS-31 remains a useful probe for cardiolipin biology at the bench. If you’re running oxidative stress models, aging models, or ischemia-reperfusion work, having SS-31 as a chemical tool lets you ask specifically whether cardiolipin stabilization is part of whatever protective phenotype you’re seeing. Thats real probe value that doesn’t depend on the clinical outcomes resolving cleanly.

What we don’t like: this peptide has been around since the early 2000s, the core mechanism literature is mature, and the Phase 3 record is mixed at best. SS-31 isn’t breaking new ground anymore; it’s validating or failing to validate an established idea in new disease contexts. For an investigator building a new research program from scratch, SS-31 is a well-characterized tool in an active space, not a frontier target. Solid mid-tier compound, genuinely important in its niche, not the first thing we’d prioritize for an undirected lab.

Novelty

55

Mechanism promise

72

In-category differentiation

65

Evidence quality

60

Translational signal

57

Research bench value

68

Rationale SS-31 earns its mid-tier placement on genuine mechanistic elegance (cardiolipin supercomplex stabilization upstream of ROS) and a real multi-indication clinical program through Stealth BioTherapeutics, but the compound’s 20-year vintage, an FDA complete response letter for geographic atrophy, and mixed Phase 3 signals pull novelty and translational scores down; bench value stays solid because it remains the reference peptide probe for cardiolipin biology and has no real structural analogue for that specific question.

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

Synthetic tetrapeptide mitochondrial-targeting cardiolipin-binding peptide

A 4-amino-acid mitochondrial-targeting peptide developed at Cornell University, characterized for binding to cardiolipin in the inner mitochondrial membrane and protecting mitochondrial function in oxidative stress.

Abstract

SS-31 (sequence D-Arg-Dmt-Lys-Phe-NH2, also known as elamipretide, Bendavia, MTP-131; CAS 736992-21-5; molecular formula C32H49N9O5; molecular weight 639.79) is a synthetic tetrapeptide developed in the laboratory of Hazel Szeto at Cornell University Medical College beginning in the early 2000s. The peptide is the most extensively characterized member of the Szeto-Schiller (SS) series of mitochondrial-targeting tetrapeptides. The biological mechanism is binding to cardiolipin in the inner mitochondrial membrane, which protects the membrane lipid environment from peroxidation, stabilizes the supercomplexes of the electron transport chain, and improves mitochondrial efficiency in conditions of oxidative stress or mitochondrial dysfunction. The compound is the active pharmaceutical ingredient in elamipretide (Bendavia), which has been advanced through Phase 2 and Phase 3 clinical trials by Stealth BioTherapeutics for primary mitochondrial myopathies, age-related macular degeneration (dry AMD with geographic atrophy), Barth syndrome, and other mitochondrial dysfunction indications. The clinical record is mixed; the most-promising results have come in Barth syndrome and primary mitochondrial myopathy. The compound is not approved by any regulatory authority for human or veterinary use as of this revision; recent FDA review in geographic atrophy resulted in a complete response letter requesting additional data. The Kodiac biolabs lot of record is SW260307, manufactured 7 March 2026 by Xian Sowu Biotech, with a vendor COA assay of 99.62 percent and a supplementary HPLC area-percent of 99.18 percent at 220 nm; both documents are archived on the lab results page.

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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 8, 2026
5-Amino-1MQ

Plain-language summaryIntrigue 72 / 100

5-Amino-1MQ is a small molecule that selectively inhibits the NNMT enzyme. NNMT degrades NAD+ precursors and methyl donors; inhibiting it boosts cellular energy and fat metabolism, with research interest in obesity and metabolic disease. Capsule format here. Stocked in the Kodiac catalog as a research-only powder for laboratory work; not a medicine, not for human consumption.

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

Our opinion on this compoundNovel, promising

59/100

Novel NNMT inhibitor with elegant dual-node mechanism and solid preclinical case, human evidence still absent

Yeah, 5-Amino-1MQ is one of the more interesting small molecules to come out of academic medicinal chemistry in the last decade. The target, nicotinamide N-methyltransferase, had been a curiosity in cancer biology for years before anyone asked whether selective inhibition might be pharmacologically useful outside the oncology context. What changed is a pair of mechanistic insights that make NNMT genuinely interesting for metabolic and aging research: the enzyme simultaneously drains nicotinamide away from the NAD+ salvage pathway and consumes SAM, the universal methyl donor. Block NNMT and you potentially shift both the cellular NAD+ pool and methylation potential in the same direction. Thats the kind of elegant dual-node mechanism that gets bench scientists interested, and it’s distinct enough from standard NAD+ precursor supplementation to justify its own research program.

The evidence base is real but you have to be honest about what it consists of. Most of it is academic rodent work, primarily adipose and skeletal muscle stem cell models. The obesity model data from the Jacobson group and related labs is reasonably well-replicated at the preclinical level, with consistent effects on body composition, adipocyte size, and metabolic markers in diet-induced obesity models. The skeletal muscle stem cell aging angle is genuinely interesting and addresses a different biology than the adipose story. The trouble is there’s essentially no human data. No IND, no phase 1 safety signal to anchor on, no pharmacokinetic data in people to confirm that the rodent predictions hold under the real constraints of human metabolism.

What we like here is that 5-Amino-1MQ is the reference compound for NNMT biology full stop. If you’re studying this target in cancer, adipose, or aging contexts, this is the tool you reach for. There isn’t a cleaner or better-characterized selective inhibitor available for in vitro or in vivo work, which gives it real bench utility that extends beyond its own pharmacological story into any program touching NAD+ biology or one-carbon metabolism.

What we dont like is the evidence maturity problem. The research record is short, the human signal is absent, and there’s a real open question about how well the rodent adipose phenotype translates. The SAM depletion axis hasn’t been fully characterized for off-target methylation effects under prolonged dosing, and that gap matters when you’re talking about a compound that touches the universal methyl donor. Until there’s more replication across independent labs and some pharmacokinetic anchoring in humans, this stays in the promising preclinical bucket.

The score lands at 59 because the target and mechanism are genuinely novel, the preclinical case is credible, and the bench utility is real, but the translational gap is wide enough that you cant call it more than that. For investigators studying NAD+ biology, adipose metabolism, or muscle stem cell aging, 5-Amino-1MQ is probably already on your list. For everyone else, worth knowing about but premature to center a research program around.

Novelty

68

Mechanism promise

72

In-category differentiation

68

Evidence quality

38

Translational signal

38

Research bench value

60

Rationale Scores well on novelty and mechanism because NNMT inhibition with dual NAD+/SAM connectivity is a genuinely recent and elegant target, and 5-Amino-1MQ is the field reference compound; evidence quality and translational signal are pulled down significantly by the short research record and total absence of human pharmacokinetic or efficacy data.

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

Small-molecule selective NNMT inhibitor (capsule format)

A 159 Da quinolinium small molecule that selectively inhibits nicotinamide N-methyltransferase, characterized for effects on adipose metabolism and skeletal muscle stem cell function. Supplied as 60 capsules x 50 mg.

Abstract

5-Amino-1-methylquinolinium iodide (5-Amino-1MQ; CAS 954126-98-8; molecular formula C11H12N2; molecular weight 159.20 for the cation; the iodide salt has additional mass) is a small-molecule selective inhibitor of nicotinamide N-methyltransferase (NNMT, EC 2.1.1.1), the enzyme that methylates nicotinamide to N1-methylnicotinamide using S-adenosylmethionine (SAM) as the methyl donor. NNMT activity diverts nicotinamide away from the NAD+ salvage pathway and consumes SAM, which connects NNMT activity to both the cellular NAD+ pool and the methylation potential of the cell. NNMT is overexpressed in many cancers (where it has been characterized as an “oncometabolic” enzyme) and in obesity-associated white adipose tissue, where it has been linked to insulin resistance and to the metabolic dysfunction phenotype. Selective NNMT inhibitors including 5-Amino-1MQ have been developed primarily by academic medicinal chemistry groups beginning in the late 2010s and have been characterized in cell culture, in vivo rodent obesity and aging models, and in skeletal muscle stem cell and aging models. The compound is supplied at Kodiac biolabs as a 60-capsule oral preparation, 50 milligrams per capsule, reflecting the small molecule’s stability and oral bioavailability. There is no FDA-approved IND for 5-Amino-1MQ in any indication. The compound is not a regulated drug substance in the United States, the European Union, or Japan. The principal limitations on the strength of the evidence are the relatively short duration of the published research record and the limited human safety and efficacy data.

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May 8, 2026

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