FGL(L)

FGL(L) at a Glance

FGL is a synthetic peptide derived from the neural cell adhesion molecule (NCAM), designed to reproduce the part of NCAM that activates the FGF receptor — the signalling step behind synaptic plasticity and neuronal survival. It was developed as a tool for studying memory and neuroprotection, and its evidence is almost entirely rodent. It is an unapproved research chemical with no human trials.

History & Development

FGL is a fragment of a cell-adhesion molecule repurposed as a growth-factor receptor activator - copying the loop that one protein uses to talk to another.

First described	Not established in the sources consulted for this section
Discovered / synthesised by	Not established in the sources consulted for this section
Institution	Not established in the sources consulted for this section
Origin	Synthetic peptide mimicking the FG loop of NCAM (neural cell adhesion molecule); FGFR1 agonist
Key patent	Not established in the sources consulted for this section
Assignee	Not established in the sources consulted for this section
Development status	Research chemical - studied almost entirely in rodents; never approved

Discovery

NCAM holds neurons together, but it also signals - and part of how it does so is by binding and activating FGFR1, the fibroblast growth factor receptor, through a specific structural feature called the FG loop.

FGL is a synthetic peptide reproducing that loop. Rather than mimicking a hormone, it mimics the interface between two proteins - activating FGFR1 directly and, downstream, facilitating AMPA-receptor synaptic delivery and quieting microglia through CD200 and IGF-1 signalling. The combination of synaptic and anti-neuroinflammatory action is what made it interesting for memory and neuroprotection.

Development & ownership

The research is almost entirely rodent, covering memory and neuroprotection, and the compound has not progressed into a human development programme.

Its position is like P21 and dihexa: a mechanistically coherent preclinical neuro-peptide with a plausible story, no human data, and a literature narrow enough that independent replication is limited.

How it reached the market

FGL moved from academic neuroscience into the research-chemical market, sold for memory and neuroprotection on rodent findings. It has never been tested in a human, has no established dose, and has no safety data by any route.

What It's Used For

FGL — also written FGLL or FGL(L), the “FG loop” peptide — is a synthetic 15-amino-acid peptide copied from the FG loop of the second fibronectin type III module of the neural cell adhesion molecule (NCAM). That loop is the surface NCAM uses to dock onto and activate fibroblast growth factor receptor 1 (FGFR1), so the peptide is designed to switch FGFR1 on directly, without NCAM–NCAM binding first ^{2Reference 2Neiiendam JL et al. · 2004In vitroAn NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons — in vitroView study →}.

The premise is elegant: a small, manufacturable peptide standing in for a large cell-adhesion protein’s receptor interaction. The first thing to be clear about is what FGL is not. “FGL” is one of the most overloaded abbreviations in biomedicine — it is also the standard abbreviation for fibrinogen-like protein 1 and 2 (FGL1/FGL2), immune checkpoint and coagulation molecules with a large, entirely unrelated oncology literature. A search on “FGL” returns mostly those papers, and none of them are about this compound. FGL is also one of several NCAM-derived mimetic peptides from the same Copenhagen laboratory — P2, C3, plannexin, FGLS — which are frequently and wrongly cited as if they were FGL ^{20Reference 20Chu C et al. · 2018ReviewNCAM mimetic peptides: potential therapeutic target for neurological disorders — reviewView study →}.

The evidence posture is preclinical and animal-only for every claimed benefit. Roughly three dozen rodent and cell-culture studies, from labs in Copenhagen, Madrid, Dublin, Cologne, Munich and Michigan, support memory enhancement, neuroprotection and an anti-inflammatory action. The only human study ever run is a 2007 Phase 1 single-dose intranasal tolerability and pharmacokinetics trial in 24 healthy men — it measured safety and plasma levels and tested no efficacy endpoint whatsoever ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}.

Route is load-bearing but not disqualifying: much of the foundational memory work used intracerebroventricular injection directly into the brain ^{3Reference 3Cambon K et al. · 2004AnimalA synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation — animal (rat)View study →}, which no person could use, but later studies used subcutaneous dosing ^{4,14,16Reference 4Secher T et al. · 2006AnimalA neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention — animal (rat)View study →Reference 14Corbett NJ et al. · 2013AnimalAmyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived peptide — animal (rat)View study →Reference 16Klein R et al. · 2014In vitroThe synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo — animal (rat) / in vitroView study →}, and an independent group has directly measured FGL in cerebrospinal fluid after peripheral dosing in both rats and non-human primates — so brain penetration is demonstrated rather than assumed ^{19Reference 19Turner CA et al. · 2019AnimalNeural cell adhesion molecule peptide mimetics modulate emotionality: pharmacokinetic and behavioral studies in rats and non-human primates — animal (rat and non-human primate); tested plannexin, FGLL and FGLSView study →}.

What the human PK shows, though, is that the numbers are tiny: a 200 mg intranasal dose produced a mean peak plasma concentration of 1.38 ng/mL ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}.

FGL is not approved anywhere, and its clinical program has been dormant for over a decade.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric. For FGL the ceiling is deliberately low: nothing here clears 40%, because every application is animal or cell-culture data with no human efficacy trial in existence. Read the low numbers carefully — for most rows they mean never tested in people, but for seizure disease-modification (not scored below, see Safety) and for acute anxiety ^{19Reference 19Turner CA et al. · 2019AnimalNeural cell adhesion molecule peptide mimetics modulate emotionality: pharmacokinetic and behavioral studies in rats and non-human primates — animal (rat and non-human primate); tested plannexin, FGLL and FGLSView study →} they mean tested and negative. Each application links down to its write-up.

01Memory & cognitive enhancementShaky40%Replicated multi-lab rat behavioral work + detailed AMPA/LTP mechanism; human data are PK/safety only, no efficacy trial ^{3,4,5,12,13Reference 3Cambon K et al. · 2004AnimalA synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation — animal (rat)View study →Reference 4Secher T et al. · 2006AnimalA neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention — animal (rat)View study →Reference 5Secher T et al. · 2009AnimalEffect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats — animal (rat)View study →Reference 12Dallérac G et al. · 2011AnimalThe neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo — animal (rat)View study →Reference 13Knafo S et al. · 2012In vitroFacilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement — animal (rat) / in vitro; the mechanism study for FGL, and the source of the ENKAM shareholding disclosureView study →}

02Neuroprotection after ischemia & strokeShaky30%Rat slice and in-vivo ischemia plus a rat MCAO stroke model, two labs; no human trial ^{6,17Reference 6Skibo GG et al. · 2005In vitroA synthetic NCAM-derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo — animal (rat) / in vitroView study →Reference 17Klein R et al. · 2016AnimalThe neural cell adhesion molecule-derived (NCAM)-peptide FG loop (FGL) mobilizes endogenous neural stem cells and promotes endogenous regenerative capacity after stroke — animal (rat)View study →}

03Alzheimer’s-model neuroprotectionShaky28%Rat amyloid-β models; the indication that drove clinical development, never read out in patients ^{7,14Reference 7Klementiev B et al. · 2007AnimalA neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35 — animal (rat)View study →Reference 14Corbett NJ et al. · 2013AnimalAmyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived peptide — animal (rat)View study →}

04Neuroinflammation & brain agingShaky26%Aged-rat and LPS models via CD200/IGF-1 — a large cluster but one overlapping author group; rodent-only ^{9,10,11,15Reference 9Downer EJ et al. · 2009AnimalA synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation — animal (rat)View study →Reference 10Downer EJ et al. · 2010AnimalA novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL — animal (rat)View study →Reference 11Ojo B et al. · 2011AnimalA neural cell adhesion molecule-derived peptide, FGL, attenuates glial cell activation in the aged hippocampus — animal (rat)View study →Reference 15Cox FF et al. · 2013AnimalThe neural cell adhesion molecule-derived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner — animal (rat)View study →}

05Neural stem-cell mobilizationShaky22%Rat NSC mobilization in vitro and in vivo, essentially a single group ^{16,17Reference 16Klein R et al. · 2014In vitroThe synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo — animal (rat) / in vitroView study →Reference 17Klein R et al. · 2016AnimalThe neural cell adhesion molecule-derived (NCAM)-peptide FG loop (FGL) mobilizes endogenous neural stem cells and promotes endogenous regenerative capacity after stroke — animal (rat)View study →}

06Mood & emotionalityShaky18%One independent rat + primate study; acutely anxiogenic, chronically antidepressant-like — a mixed result, and the authors favored a different peptide ^{19Reference 19Turner CA et al. · 2019AnimalNeural cell adhesion molecule peptide mimetics modulate emotionality: pharmacokinetic and behavioral studies in rats and non-human primates — animal (rat and non-human primate); tested plannexin, FGLL and FGLSView study →}

07Neurite outgrowth & neuronal survivalShaky16%Foundational cell-culture pharmacology; establishes mechanism, not benefit ^{1,2Reference 1Soroka V et al. · 2002In vitroInduction of neuronal differentiation by a peptide corresponding to the homophilic binding site of the second Ig module of the neural cell adhesion molecule — in vitro (this study tested P2, the sibling NCAM peptide, not FGL; cited for lineage only)View study →Reference 2Neiiendam JL et al. · 2004In vitroAn NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons — in vitroView study →}

Mechanisms

Pharmacokinetics

FGL is a peptide with negligible oral bioavailability and was never developed as an oral drug; any oral “FGL” product is pharmacologically inert regardless of the label. Preclinical work delivered it subcutaneously, intracerebroventricularly, or intranasally, and PK studies in rats, dogs and monkeys showed measurable exposure in both plasma and cerebrospinal fluid after parenteral or intranasal dosing with no systemic toxicity ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}. Brain penetration after peripheral dosing has since been measured directly rather than assumed: cisternal CSF concentrations correlated with plasma concentrations in rats and non-human primates, with comparable CSF-to-blood ratios in both species ^{19Reference 19Turner CA et al. · 2019AnimalNeural cell adhesion molecule peptide mimetics modulate emotionality: pharmacokinetic and behavioral studies in rats and non-human primates — animal (rat and non-human primate); tested plannexin, FGLL and FGLSView study →}.

The human numbers are the sobering part. In the Phase 1 study, single intranasal doses of 25, 100 and 200 mg produced dose-related but extremely low systemic exposure: plasma peptide was undetectable at every timepoint at 25 mg, quantifiable for about 1 hour at 100 mg and about 4 hours at 200 mg, with mean C_max of 0.52 and 1.38 ng/mL and mean AUC24 of 1.27 and 4.05 ng·h/mL for the 100 and 200 mg doses respectively ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}. A 200-milligram dose yielding a nanogram-per-milliliter peak is a very inefficient delivery, consistent with a 15-residue peptide crossing nasal mucosa. The clinical candidate FGL(L) is a dendrimeric form — two FGL peptide arms on a lysine core — built for stability, and it is not established that gray-market “FGL” is the same construct. A later formulation study conjugated the peptide to hyaluronate specifically to slow nasal clearance and improve nose-to-brain transport ^{21Reference 21Kim YS et al. · 2019AnimalNose-to-brain delivery of hyaluronate — FG loop peptide conjugate for non-invasive hypoxic-ischemic encephalopathy therapy — animal (rat)View study →}. Human half-life, repeat-dose pharmacokinetics, absolute bioavailability, and human brain exposure are all unestablished.

Clinical & regulatory status

FGL is an unapproved investigational peptide — never approved by the FDA, EMA, TGA or any other regulator, and not a lawful dietary supplement anywhere. Its furthest verified milestone is the 2007 Phase 1 open-label, single-ascending-dose intranasal study in 24 healthy men, run while it was in clinical development for neurodegenerative disease; that paper stated further studies in Alzheimer’s patients were “currently being planned” ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}.

The commercial history is worth tracing, because the peptide’s discoverers were also its commercial owners. FGL was licensed to ENKAM Pharmaceuticals A/S (Copenhagen); the conflict-of-interest statement on the key mechanism paper records that Elisabeth Bock and Vladimir Berezin were ENKAM shareholders and that ENKAM owned the FGL peptide ^{13Reference 13Knafo S et al. · 2012In vitroFacilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement — animal (rat) / in vitro; the mechanism study for FGL, and the source of the ENKAM shareholding disclosureView study →}. Development continued at least into 2014 — an independent group writing that year described FGL as “currently in clinical development for neurodegenerative diseases and brain insults” ^{18Reference 18Zellinger C et al. · 2014AnimalImpact of the neural cell adhesion molecule-derived peptide FGL on seizure progression and cellular alterations in the mouse kindling model — animal (mouse); negative result — accelerated seizure developmentView study →}. The program’s last documented push was NEUROFGL, an EU Seventh Framework Program project coordinated by the University of Copenhagen, which ran 1 January 2012 to 31 December 2014 on a total budget of roughly €7.8 million with an EU contribution of about €6.0 million (European Commission CORDIS project record). The CORDIS results summary reports preclinical findings and a single-ascending-dose safety and tolerability study, and reports no efficacy outcome in patients.

Two things then have to be said carefully. First, no trial of FGL, FGLL or any NCAM mimetic peptide is registered on ClinicalTrials.gov or the EU Clinical Trials Register — searches on “FGL”, “FGLL”, “FG loop peptide” and “ENKAM” return only unrelated records (facial gingival level surgery, fingolimod, a multiple-sclerosis comparison trial). Second, some secondary company-profile material claims ENKAM ran three Phase 1 studies, a Phase 2a in Alzheimer’s patients, and a stroke pilot. That claim is not corroborated by the CORDIS project record, by either trial registry, or by any publication located in this pass, and it is recorded here as an unverified secondary claim rather than a finding. On the evidence available, one Phase 1 study is what exists in the literature.

The program has been dormant since NEUROFGL closed at the end of 2014, and the newest primary literature on the compound is from 2019. No primary source states why development stopped. Funding exhaustion at the end of a fixed-term EU grant, with no positive patient readout to raise against, is a reasonable inference — but it is an inference, and it is not documented fact. Today FGL is sold only by research-chemical vendors, labeled “not for human consumption.”

Last checked: July 2026.

Sourcing, Route & Legal Status

Regulatory status. FGL has never held a marketing approval in any jurisdiction — there is no approved product, no withdrawn approval, and no prescription status anywhere to point at. It is not a scheduled or controlled substance, but “not scheduled” is not “approved”: there is no legal pathway for human therapeutic use, and marketing it for human consumption is unlawful in most Western jurisdictions. Every unit in circulation is sold on the research-chemical model — labeled “for research use only / not for human consumption” while being marketed, in practice, to people who intend to take it for cognition.

How it’s supplied & administered. Sold as a lyophilized (freeze-dried) powder requiring reconstitution, usually with bacteriostatic water. Because oral bioavailability is negligible, the routes with any published basis are subcutaneous injection and intranasal delivery; oral capsules cannot deliver intact peptide. Lyophilized peptide is generally stored cold and protected from light, and reconstituted solution is short-lived — but no stability or shelf-life data exists for the specific product being sold.

Sourcing reality (a safety issue, not a footnote). The generic gray-market risks apply in full: unregulated manufacture, no oversight, and real potential for incorrect identity, low purity, and bacterial endotoxin contamination — the last especially serious for an injected product, and pointedly relevant here, since the compound’s own selling point is that it reduces neuroinflammation.

Two risks are worse for FGL than for a typical gray-market peptide, and they are the practical bottom line of this section:

• Almost nothing is sold, so almost nothing is tested. FGL is an obscure compound with few vendors and correspondingly little independent third-party testing. The pooled community COA data that partly constrains the market for a high-volume peptide simply does not exist here.
• There is no reference standard a buyer can check against. With no approved product and no pharmacopoeial monograph, a buyer has nothing authoritative to compare a certificate of analysis to. Worse, the published clinical material was the dendrimeric FGL(L) construct, while vendors generally sell an unspecified “FGL” — so even a correct peptide may not be the molecule the research was done on. Identity here is not a theoretical concern; it is unresolvable with the information available to a purchaser.

This page does not recommend or link vendors.

Safety

The entire human safety database for FGL is one single-dose study in 24 men — and the most important finding on record is preclinical: in a mouse kindling model, FGL accelerated the development of seizures.

Safety at a Glance

❔ Toxicity unknown

• A pro-convulsant signal in mice. Both doses tested reduced the stimulation needed to induce a generalized seizure — disqualifying with any seizure or head-injury history.
• One single dose is the whole human safety record. 24 healthy men, one intranasal dose, no follow-up — it says nothing about repeated use, which is how people actually take it.
• Never assessed in pregnancy or breastfeeding. No human or animal reproductive data — see the box below.
• Acutely anxiogenic in rats and primates. An adverse behavioral effect from the same work usually cited as proof it acts systemically.
• Active or past malignancy. Its core action is growth-factor receptor agonism, and no carcinogenicity assessment exists.
• Interactions have never been assessed, anywhere. Co-use with anything that lowers seizure threshold is a specific theoretical concern.

Full Safety & Interactions Detail

Overall posture. The entire human safety database for FGL is one single-dose study: 24 healthy men, single intranasal doses of 25, 100 and 200 mg. All three doses were well tolerated with no clinically notable abnormalities in ECG, vital signs or laboratory tests. Five adverse events occurred in three subjects (13%): a transient burning sensation in the nose lasting under three minutes in two subjects at 200 mg, and brief runny eyes in one subject at 25 mg — both immediately post-dose and suspected drug-related. One subject additionally reported dizziness, vomiting and headache with onset more than two days later, judged unrelated ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}. That is everything: single dose, healthy young-to-middle-aged men, no repeat dosing, no patient population, no follow-up. It says nothing about the safety of taking this compound repeatedly, which is the only way anyone actually uses it.

The pro-convulsant signal — the most important adverse finding on record. In a mouse kindling model, both doses tested (2 and 10 mg/kg) significantly reduced the number of stimulations needed to induce a generalized seizure — that is, FGL accelerated the development of seizures. The study was designed to test whether FGL was disease-modifying in epilepsy; it concluded the opposite, with the authors stating the results “raise some concern regarding a putative effect, which might promote the formation of a hyperexcitable network,” and calling for risk assessment in models of spontaneous seizures ^{18Reference 18Zellinger C et al. · 2014AnimalImpact of the neural cell adhesion molecule-derived peptide FGL on seizure progression and cellular alterations in the mouse kindling model — animal (mouse); negative result — accelerated seizure developmentView study →}. The effect is mechanistically plausible — FGFR and plasticity signaling can lower seizure threshold — which makes it harder to dismiss as a model artifact. Anyone with a seizure history, a head-injury history, or on a medication that lowers seizure threshold should treat this as disqualifying rather than as a caveat.

Other animal signals. Preclinical toxicology in rats, dogs and monkeys reported no systemic toxicity at the exposures tested ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}. But the independent rat and primate study found FGLL acutely anxiogenic ^{19Reference 19Turner CA et al. · 2019AnimalNeural cell adhesion molecule peptide mimetics modulate emotionality: pharmacokinetic and behavioral studies in rats and non-human primates — animal (rat and non-human primate); tested plannexin, FGLL and FGLSView study →} — an adverse behavioral effect, in the same paper usually cited as evidence the compound works systemically.

Interactions have not been assessed in humans, in animals, or at all. On mechanism, a systemic FGFR1 agonist could in principle interact with other growth-factor or plasticity-active agents, and the seizure finding makes co-use with anything affecting seizure threshold a specific theoretical concern — but this is class-level reasoning, explicitly not a tested interaction. Route-specific risks follow from the research-chemical reality: injection-site reactions, and, driven by unregulated sourcing, sterility failure and endotoxin exposure.

Who should avoid it. Anyone with epilepsy or any seizure history; anyone pregnant, breastfeeding or trying to conceive; anyone with an active or historical malignancy, given that the compound’s core action is agonism at a growth-factor receptor and no carcinogenicity assessment exists; and anyone unwilling to accept a product whose identity cannot be verified.

Scope disclosure (honesty, not a claim):

• Human data? Minimal, and only safety — a single Phase 1 single-dose intranasal tolerability and PK study. There is no human efficacy data for any application here.
• Interactions assessed? No. Not evaluated in humans or animals; only mechanism-level speculation is offered, and it is labeled as such.
• Pregnancy/lactation assessed? No — no human or animal reproductive data located.
• Long-term safety established? No. Only single-dose human data exists; repeat-dose and chronic safety are entirely unknown, and no carcinogenicity assessment has been published for a compound that agonizes a growth-factor receptor.

Never imply safety from silence. Where FGL has not been studied — repeat dosing, interactions, pregnancy, long-term use, gray-market product identity — the correct statement is “not assessed,” not “safe.” And where it has been studied and the result was bad, as with seizure kindling, that is a finding, not an absence.

Pregnancy & Lactation

? Not established in pregnancy? Not established in lactation

Not assessed / not established. No human pregnancy or lactation data and no dedicated reproductive-toxicity study was located. Treat as contraindicated by default.

Dosage

There is no established human dose for FGL, and none is recommended here. It has no approved indication anywhere, and no human study has ever tested it for effect, so there is no dose-response data from which a therapeutic amount could be derived.

The only human figures that exist are the tolerability doses from the Phase 1 study: single intranasal doses of 25, 100 and 200 mg ^{8Reference 8Anand R et al. · 2007Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24)View study →}. Those are reported here as data, not as a protocol. They were administered once each, under medical supervision, to establish tolerability and measure plasma levels — not to produce an effect, and not repeatedly. Note what they showed: at 25 mg the peptide was undetectable in plasma at every timepoint, so the lower end of that ladder did not achieve measurable systemic exposure at all. Rodent efficacy studies typically dosed in the range of a few milligrams per kilogram subcutaneously; animal doses do not translate to human doses, and the mouse study at 2 and 10 mg/kg is the one that accelerated seizures ^{18Reference 18Zellinger C et al. · 2014AnimalImpact of the neural cell adhesion molecule-derived peptide FGL on seizure progression and cellular alterations in the mouse kindling model — animal (mouse); negative result — accelerated seizure developmentView study →}.

Oral FGL cannot deliver intact peptide regardless of what a label claims (see Pharmacokinetics). This entry is informational only and is not an endorsement of use.

References

1. Soroka V, Kiryushko D, Novitskaya V, et al. (2002). Induction of neuronal differentiation by a peptide corresponding to the homophilic binding site of the second Ig module of the neural cell adhesion molecule — in vitro (this study tested P2, the sibling NCAM peptide, not FGL; cited for lineage only). J Biol Chem. https://pubmed.ncbi.nlm.nih.gov/11983682/
2. Neiiendam JL, Køhler LB, Christensen C, et al. (2004). An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons — in vitro. J Neurochem. https://pubmed.ncbi.nlm.nih.gov/15525346/
3. Cambon K, Hansen SM, Venero C, et al. (2004). A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation — animal (rat). J Neurosci. https://pubmed.ncbi.nlm.nih.gov/15115815/
4. Secher T, Novitskaia V, Berezin V, et al. (2006). A neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention — animal (rat). Neuroscience. https://pubmed.ncbi.nlm.nih.gov/16784819/
5. Secher T, Berezin V, Bock E, Glenthøj B. (2009). Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats — animal (rat). Behav Brain Res. https://pubmed.ncbi.nlm.nih.gov/19133297/
6. Skibo GG, Lushnikova IV, Voronin KY, et al. (2005). A synthetic NCAM-derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo — animal (rat) / in vitro. Eur J Neurosci. https://pubmed.ncbi.nlm.nih.gov/16197499/
7. Klementiev B, Novikova T, Novitskaya V, et al. (2007). A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35 — animal (rat). Neuroscience. https://pubmed.ncbi.nlm.nih.gov/17223274/
8. Anand R, Seiberling M, Kamtchoua T, Pokorny R. (2007). Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers — human (Phase 1, open-label single ascending dose, n=24). Clin Pharmacokinet. https://pubmed.ncbi.nlm.nih.gov/17375985/
9. Downer EJ, Cowley TR, Cox F, et al. (2009). A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation — animal (rat). J Neurochem. https://pubmed.ncbi.nlm.nih.gov/19457161/
10. Downer EJ, Cowley TR, Lyons A, et al. (2010). A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL — animal (rat). Neurobiol Aging. https://pubmed.ncbi.nlm.nih.gov/18468731/
11. Ojo B, Rezaie P, Gabbott PL, et al. (2011). A neural cell adhesion molecule-derived peptide, FGL, attenuates glial cell activation in the aged hippocampus — animal (rat). Exp Neurol. https://pubmed.ncbi.nlm.nih.gov/21978973/
12. Dallérac G, Zerwas M, Novikova T, et al. (2011). The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo — animal (rat). Learn Mem. https://pubmed.ncbi.nlm.nih.gov/21508096/
13. Knafo S, Venero C, Sánchez-Puelles C, et al. (2012). Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement — animal (rat) / in vitro; the mechanism study for FGL, and the source of the ENKAM shareholding disclosure. PLoS Biol. https://pubmed.ncbi.nlm.nih.gov/22363206/
14. Corbett NJ, Gabbott PL, Klementiev B, et al. (2013). Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived peptide — animal (rat). PLoS One. https://pubmed.ncbi.nlm.nih.gov/23951173/
15. Cox FF, Berezin V, Bock E, Lynch MA. (2013). The neural cell adhesion molecule-derived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner — animal (rat). Neuroscience. https://pubmed.ncbi.nlm.nih.gov/23337536/
16. Klein R, Blaschke S, Neumaier B, et al. (2014). The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo — animal (rat) / in vitro. Stem Cell Rev Rep. https://pubmed.ncbi.nlm.nih.gov/24817672/
17. Klein R, Mahlberg N, Ohren M, et al. (2016). The neural cell adhesion molecule-derived (NCAM)-peptide FG loop (FGL) mobilizes endogenous neural stem cells and promotes endogenous regenerative capacity after stroke — animal (rat). J Neuroimmune Pharmacol. https://pubmed.ncbi.nlm.nih.gov/27352075/
18. Zellinger C, Salvamoser JD, Seeger N, et al. (2014). Impact of the neural cell adhesion molecule-derived peptide FGL on seizure progression and cellular alterations in the mouse kindling model — animal (mouse); negative result — accelerated seizure development. ACS Chem Neurosci. https://pubmed.ncbi.nlm.nih.gov/24456603/
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