FGL peptide

updated

FGL is a synthetic 15-amino-acid peptide matching the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. In rats it improved memory after injection into the brain ventricles. No controlled human study exists: the only human data are a single-dose phase 1 study in 24 healthy men that measured tolerability and plasma levels, and a PubMed search on 9 October 2026 found no efficacy trial in any human population.

Neural cell adhesion molecule (NCAM) mimetic peptide acting on FGF receptor 1

  • PubChem lists FGL peptide as CID 16200289, C71H116N20O25, molecular weight 1649.8, CAS 499993-62-3; the published work also uses related but distinct preparations (FGL(L), FGLL, FGLS and plannexin) that behave differently in rats.
  • In rats, injection of FGL into the brain ventricles immediately after training induced a long-lasting improvement of memory; this was not a peripheral dose.
  • In young adult rats without injury, FGL caused a 40% decrease in CA1 pyramidal cells, the same size as the loss from the amyloid-beta insult it partly alleviated.
  • In a phase 1 study of 24 healthy men, single intranasal doses of FGL(L) were well tolerated; three subjects (13%) reported five adverse events, and no cognitive, protective or anti-inflammatory outcome was measured.
  • A PubMed search on 9 October 2026 restricted to clinical trial or randomized controlled trial publication types returned 1 record, the 2007 phase 1 study.
  • No study in the records reviewed combined FGL with SS-31, methylene blue or dihexa.

What is FGL, and is it approved for anything?

FGL is a synthetic 15-amino-acid peptide that matches the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. No approval for any use appears in the records reviewed.

FGL peptide, the FG loop peptide, is a synthetic 15-amino-acid peptide corresponding to the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. PubChem lists it as CID 16200289, C71H116N20O25, molecular weight 1649.8, CAS 499993-62-3.

A PubMed search on 9 October 2026 for FGL peptide, FG loop peptide or FGLL restricted to clinical trial or randomized controlled trial publication types returned 1 record, a phase 1 study. A ClinicalTrials.gov query for NCAM mimetic peptide Alzheimer returned no studies. No approval for any use appears in the records reviewed.

PubChem: FGL peptide identity, 15-mer

Chemical identity record

National Library of Medicine. PubChem compound record CID 16200289 (FGL peptide).

FGL peptide, the FG loop peptide, is a synthetic 15-amino-acid peptide corresponding to the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. PubChem lists it as CID 16200289, C71H116N20O25, molecular weight 1649.8, CAS 499993-62-3.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic 15-mer
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The PubChem record is for FGL peptide. The human data on this page are for FGL(L), and other studies used plannexin, FGLL and FGLS, so a record or result for one preparation does not automatically describe another.

Read the original source
Searches, 9 October 2026: one clinical trial record, the phase 1 study; no efficacy trial

PubMed search record

PubMed search run on 9 October 2026: (FGL peptide OR FG loop peptide OR FGLL) restricted to clinical trial or randomized controlled trial publication types, 1 record. A second PubMed search for FGLL or FGL(L) with Alzheimer or patients. ClinicalTrials.gov queries run the same day.

The search restricted to clinical trial or randomized controlled trial publication types returned 1 record, the 2007 phase 1 study. A PubMed search for FGLL or FGL(L) with Alzheimer or patients returned the same single record, so the Alzheimer patient studies that the 2007 authors said were being planned do not appear in PubMed 19 years later. A ClinicalTrials.gov query for NCAM mimetic peptide Alzheimer returned no studies, and a query for FGLL returned 2 studies, both unrelated (a pediatric cancer care platform and a children's spiritual diary study). The records reviewed contain no efficacy trial of FGL for any condition and no repeat-dose human safety data.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

Is every study of FGL a study of the same preparation?

No. The PubChem record is for FGL peptide, the human data are for FGL(L), and a 2019 rat study found that plannexin, FGLL and FGLS each behave differently. A product labeled FGL is not automatically the preparation behind any given result.

The published work uses several related but distinct preparations. The 15-mer in the PubChem record is FGL peptide. The phase 1 study used FGL(L). A 2019 study tested the NCAM mimetics plannexin, FGLL and FGLS side by side in rats and found a different profile for each.

Plannexin acutely increased and chronically decreased anxiety, with no antidepressant effect. FGLL had acute anxiogenic effects and chronic antidepressant effects. FGLS had antidepressant effects without modulating anxiety-like behavior, and those effects were blocked by an AMPA receptor antagonist.

In PubMed the string FGL also indexes fibrinogen-like protein 1 and fibrinogen-like protein 2, which are unrelated molecules, so secondary sources citing FGL studies should be read against the molecule actually studied.

2019 comparison: plannexin, FGLL and FGLS behave differently; CSF tracks plasma in rats and primates

Animal study

Turner CA et al. Neuropsychopharmacology. 2019;44(2):356-363. PMID 29703997.

A 2019 study tested the NCAM mimetics plannexin, FGLL and FGLS side by side and found different profiles for each. Plannexin acutely increased and chronically decreased anxiety with no antidepressant effect in rats; FGLL had acute anxiogenic effects and chronic antidepressant effects; FGLS had antidepressant effects without modulating anxiety-like behavior, and those effects were blocked by an AMPA receptor antagonist. Cisternal cerebrospinal fluid levels of the FGLs correlated with blood plasma levels in rats and non-human primates, and the CSF-to-blood ratios of FGLS were comparable in both species.

Participants / model
Rats and non-human primates
Treatment
Peripheral administration of NCAM peptide mimetics; CSF and plasma sampling
Follow-up
Acute and chronic dosing; durations not stated in the available record
Study design
Original preclinical study
Funding
not stated in the source

A product labeled FGL is not automatically the preparation that produced any given result. In PubMed the string FGL also indexes fibrinogen-like protein 1 and fibrinogen-like protein 2, which are unrelated molecules, so secondary sources citing FGL studies should be read against the molecule actually studied.

Read the original source
PubChem: FGL peptide identity, 15-mer

Chemical identity record

National Library of Medicine. PubChem compound record CID 16200289 (FGL peptide).

FGL peptide, the FG loop peptide, is a synthetic 15-amino-acid peptide corresponding to the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. PubChem lists it as CID 16200289, C71H116N20O25, molecular weight 1649.8, CAS 499993-62-3.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic 15-mer
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The PubChem record is for FGL peptide. The human data on this page are for FGL(L), and other studies used plannexin, FGLL and FGLS, so a record or result for one preparation does not automatically describe another.

Read the original source
Phase 1: 24 healthy men, single intranasal doses, tolerability and plasma levels

Clinical trial

Anand R et al. Clin Pharmacokinet. 2007;46(4):351-8. PMID 17375985.

All three single intranasal doses were well tolerated, with no clinically notable abnormalities in ECG, vital signs or laboratory tests. Three subjects (13%) reported five adverse events: a transient burning sensation in the nose lasting under 3 minutes in two subjects at 200 mg, and runny eyes lasting under 2 minutes in one subject at 25 mg; one of those subjects also had dizziness, vomiting and headache starting more than 2 days after dosing, which was not judged related to the drug. Plasma concentrations were quantifiable up to 1 hour after the 100 mg dose and up to 4 hours after the 200 mg dose, and were undetectable at all timepoints at 25 mg. Mean Cmax was 0.52 ng/mL at 100 mg and 1.38 ng/mL at 200 mg; mean AUC(24) was 1.27 and 4.05 ng.h/mL.

Participants / model
24 healthy male volunteers (mean age 42, range 24 to 55)
Treatment
Single intranasal doses of FGL(L) of 25, 100 and 200 mg in sequential cohorts
Follow-up
8 days
Study design
Open-label phase 1 single ascending dose study
Funding
not stated in the source

This is a single-dose tolerability and pharmacokinetic study in healthy men. It measured no cognitive, protective or anti-inflammatory outcome. The doses are what the study gave, not an established or suggested amount.

Read the original source

What did the one study in healthy men measure?

A single-dose phase 1 study in 24 healthy men found intranasal FGL(L) well tolerated, with plasma levels quantifiable at the two higher doses. It measured no cognitive, protective or anti-inflammatory outcome, and no efficacy trial in any human population exists.

The only human data located are from an 8-day open-label phase 1 study in 24 healthy male volunteers, mean age 42 and range 24 to 55. They received single ascending intranasal doses of FGL(L) of 25, 100 and 200 mg in sequential cohorts. All three doses were well tolerated, with no clinically notable abnormalities in ECG, vital signs or laboratory tests.

Plasma concentrations were quantifiable up to 1 hour after the 100 mg dose and up to 4 hours after the 200 mg dose, and were undetectable at all timepoints at 25 mg. Mean Cmax was 0.52 ng/mL at 100 mg and 1.38 ng/mL at 200 mg, and mean AUC(24) was 1.27 and 4.05 ng.h/mL. These were single doses in a tolerability study. They describe what the study gave, not an established or suggested amount.

The study measured no cognitive, protective or anti-inflammatory outcome. A PubMed search on 9 October 2026 restricted to clinical trial or randomized controlled trial publication types returned this one record, and a search for FGLL or FGL(L) with Alzheimer or patients returned the same record, so the Alzheimer patient studies the authors said were being planned do not appear in PubMed 19 years later. The records reviewed contain no efficacy trial of FGL for any condition and no repeat-dose human safety data.

Phase 1: 24 healthy men, single intranasal doses, tolerability and plasma levels

Clinical trial

Anand R et al. Clin Pharmacokinet. 2007;46(4):351-8. PMID 17375985.

All three single intranasal doses were well tolerated, with no clinically notable abnormalities in ECG, vital signs or laboratory tests. Three subjects (13%) reported five adverse events: a transient burning sensation in the nose lasting under 3 minutes in two subjects at 200 mg, and runny eyes lasting under 2 minutes in one subject at 25 mg; one of those subjects also had dizziness, vomiting and headache starting more than 2 days after dosing, which was not judged related to the drug. Plasma concentrations were quantifiable up to 1 hour after the 100 mg dose and up to 4 hours after the 200 mg dose, and were undetectable at all timepoints at 25 mg. Mean Cmax was 0.52 ng/mL at 100 mg and 1.38 ng/mL at 200 mg; mean AUC(24) was 1.27 and 4.05 ng.h/mL.

Participants / model
24 healthy male volunteers (mean age 42, range 24 to 55)
Treatment
Single intranasal doses of FGL(L) of 25, 100 and 200 mg in sequential cohorts
Follow-up
8 days
Study design
Open-label phase 1 single ascending dose study
Funding
not stated in the source

This is a single-dose tolerability and pharmacokinetic study in healthy men. It measured no cognitive, protective or anti-inflammatory outcome. The doses are what the study gave, not an established or suggested amount.

Read the original source
Searches, 9 October 2026: one clinical trial record, the phase 1 study; no efficacy trial

PubMed search record

PubMed search run on 9 October 2026: (FGL peptide OR FG loop peptide OR FGLL) restricted to clinical trial or randomized controlled trial publication types, 1 record. A second PubMed search for FGLL or FGL(L) with Alzheimer or patients. ClinicalTrials.gov queries run the same day.

The search restricted to clinical trial or randomized controlled trial publication types returned 1 record, the 2007 phase 1 study. A PubMed search for FGLL or FGL(L) with Alzheimer or patients returned the same single record, so the Alzheimer patient studies that the 2007 authors said were being planned do not appear in PubMed 19 years later. A ClinicalTrials.gov query for NCAM mimetic peptide Alzheimer returned no studies, and a query for FGLL returned 2 studies, both unrelated (a pediatric cancer care platform and a children's spiritual diary study). The records reviewed contain no efficacy trial of FGL for any condition and no repeat-dose human safety data.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

What did the rat studies find?

Injection into the brain ventricles improved memory in rats, FGL restored hippocampal IGF-1 and lowered interferon-gamma in aged rats, and systemic FGL protected against an amyloid-beta insult. In young rats without injury, FGL caused a 40% loss of CA1 pyramidal cells.

Intracerebroventricular administration of FGL immediately after training rats in fear conditioning or water maze learning induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced presynaptic function through activation of FGFR1 and promoted synapse formation. This is the founding result for the plasticity claim, and it was produced by direct injection into the brain ventricles, not by a peripheral dose.

In aged rats, FGL reversed the age-related decline in hippocampal insulin-like growth factor-1 and abrogated the age-related increase in interferon-gamma. It also promoted IGF-1 release from primary neurons, with IGF-1 pivotal in FGL induction of neuronal Akt phosphorylation and CD200 ligand expression. This is a hippocampal glial and cytokine result in aged rats, not an anti-inflammatory result in people.

Young adult rats given amyloid-beta(25-35) into the right lateral ventricle showed impaired social recognition memory at 24 days, and systemic FGL treatment prevented the impairment. Amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 that FGL partially alleviated. However, FGL treatment without amyloid-beta also caused a 40% decrease in CA1 pyramidal cells. The authors concluded that FGL is potentially disruptive in non-pathological conditions while being neuroprotective in disease-like conditions.

In the 2019 comparison, cisternal cerebrospinal fluid levels of the FGLs correlated with blood plasma levels in rats and non-human primates, and the CSF-to-blood ratios of FGLS were comparable in both species.

Founding plasticity result: rats, injection into the brain ventricles, long-lasting memory improvement

Animal study

Cambon K et al. J Neurosci. 2004;24(17):4197-204. PMID 15115815.

Intracerebroventricular administration of FGL immediately after training rats in fear conditioning or water maze learning induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced presynaptic function through activation of FGFR1 and promoted synapse formation.

Participants / model
Rats; primary rat hippocampal neuron cultures
Treatment
Intracerebroventricular injection in vivo; media exposure in vitro
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the founding result for the plasticity claim, and it was produced by direct injection into the brain ventricles, not by a peripheral dose.

Read the original source
Aged rats: IGF-1 restored, interferon-gamma increase abrogated in hippocampus

Animal study

Downer EJ et al. J Neurochem. 2009;109(5):1516-25. PMID 19457161.

FGL reversed the age-related decline in hippocampal insulin-like growth factor-1 and abrogated the age-related increase in interferon-gamma, and it promoted IGF-1 release from primary neurons, with IGF-1 pivotal in FGL induction of neuronal Akt phosphorylation and CD200 ligand expression.

Participants / model
Aged rats; primary rat neurons
Treatment
FGL administration as dosed in the report; route not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is a hippocampal glial and cytokine result in aged rats, not an anti-inflammatory result in people.

Read the original source
Injured and uninjured young rats: protection after amyloid-beta, 40% CA1 loss without it

Animal study

Corbett NJ et al. PLoS One. 2013;8(8):e71479. PMID 23951173.

Young adult rats given amyloid-beta(25-35) into the right lateral ventricle showed impaired social recognition memory at 24 days, and this impairment was prevented by systemic FGL treatment. Amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 that FGL partially alleviated. However, FGL treatment without amyloid-beta also caused a 40% decrease in CA1 pyramidal cells. The authors concluded that FGL is potentially disruptive in non-pathological conditions while being neuroprotective in disease-like conditions.

Participants / model
Young adult rats, injured and uninjured
Treatment
Systemic FGL treatment; amyloid-beta(25-35) injected into the right lateral ventricle
Follow-up
Social recognition memory tested at 24 days
Study design
Original preclinical study with stereological cell counts
Funding
not stated in the source

This is the one study that tested uninjured animals, and it found cell loss rather than protection. That is the opposite of what a healthy user is buying.

Read the original source
2019 comparison: plannexin, FGLL and FGLS behave differently; CSF tracks plasma in rats and primates

Animal study

Turner CA et al. Neuropsychopharmacology. 2019;44(2):356-363. PMID 29703997.

A 2019 study tested the NCAM mimetics plannexin, FGLL and FGLS side by side and found different profiles for each. Plannexin acutely increased and chronically decreased anxiety with no antidepressant effect in rats; FGLL had acute anxiogenic effects and chronic antidepressant effects; FGLS had antidepressant effects without modulating anxiety-like behavior, and those effects were blocked by an AMPA receptor antagonist. Cisternal cerebrospinal fluid levels of the FGLs correlated with blood plasma levels in rats and non-human primates, and the CSF-to-blood ratios of FGLS were comparable in both species.

Participants / model
Rats and non-human primates
Treatment
Peripheral administration of NCAM peptide mimetics; CSF and plasma sampling
Follow-up
Acute and chronic dosing; durations not stated in the available record
Study design
Original preclinical study
Funding
not stated in the source

A product labeled FGL is not automatically the preparation that produced any given result. In PubMed the string FGL also indexes fibrinogen-like protein 1 and fibrinogen-like protein 2, which are unrelated molecules, so secondary sources citing FGL studies should be read against the molecule actually studied.

Read the original source

Do the plasticity, neuroprotection and anti-inflammatory claims hold up?

Only in rats, and only in part. Plasticity is supported after injection into the brain ventricles, anti-inflammatory activity in aged rat hippocampus, and neuroprotection only in injury models. No human outcome of any kind supports the claim.

Sellers describe FGL for neuroprotection, synaptic plasticity and neural anti-inflammatory support, used alongside SS-31, methylene blue or dihexa.

Synaptic plasticity is supported in rats, by injection into the brain ventricles, not by a peripheral dose. Neural anti-inflammatory activity is supported in aged rat hippocampus. Neuroprotection is supported only in injury models, and the one study that tested uninjured animals found cell loss rather than protection.

No efficacy trial of FGL exists in any human population, and no study in the records reviewed combined FGL with SS-31, methylene blue or dihexa, so the page makes no stacking claim.

Founding plasticity result: rats, injection into the brain ventricles, long-lasting memory improvement

Animal study

Cambon K et al. J Neurosci. 2004;24(17):4197-204. PMID 15115815.

Intracerebroventricular administration of FGL immediately after training rats in fear conditioning or water maze learning induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced presynaptic function through activation of FGFR1 and promoted synapse formation.

Participants / model
Rats; primary rat hippocampal neuron cultures
Treatment
Intracerebroventricular injection in vivo; media exposure in vitro
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the founding result for the plasticity claim, and it was produced by direct injection into the brain ventricles, not by a peripheral dose.

Read the original source
Aged rats: IGF-1 restored, interferon-gamma increase abrogated in hippocampus

Animal study

Downer EJ et al. J Neurochem. 2009;109(5):1516-25. PMID 19457161.

FGL reversed the age-related decline in hippocampal insulin-like growth factor-1 and abrogated the age-related increase in interferon-gamma, and it promoted IGF-1 release from primary neurons, with IGF-1 pivotal in FGL induction of neuronal Akt phosphorylation and CD200 ligand expression.

Participants / model
Aged rats; primary rat neurons
Treatment
FGL administration as dosed in the report; route not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is a hippocampal glial and cytokine result in aged rats, not an anti-inflammatory result in people.

Read the original source
Injured and uninjured young rats: protection after amyloid-beta, 40% CA1 loss without it

Animal study

Corbett NJ et al. PLoS One. 2013;8(8):e71479. PMID 23951173.

Young adult rats given amyloid-beta(25-35) into the right lateral ventricle showed impaired social recognition memory at 24 days, and this impairment was prevented by systemic FGL treatment. Amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 that FGL partially alleviated. However, FGL treatment without amyloid-beta also caused a 40% decrease in CA1 pyramidal cells. The authors concluded that FGL is potentially disruptive in non-pathological conditions while being neuroprotective in disease-like conditions.

Participants / model
Young adult rats, injured and uninjured
Treatment
Systemic FGL treatment; amyloid-beta(25-35) injected into the right lateral ventricle
Follow-up
Social recognition memory tested at 24 days
Study design
Original preclinical study with stereological cell counts
Funding
not stated in the source

This is the one study that tested uninjured animals, and it found cell loss rather than protection. That is the opposite of what a healthy user is buying.

Read the original source
Searches, 9 October 2026: one clinical trial record, the phase 1 study; no efficacy trial

PubMed search record

PubMed search run on 9 October 2026: (FGL peptide OR FG loop peptide OR FGLL) restricted to clinical trial or randomized controlled trial publication types, 1 record. A second PubMed search for FGLL or FGL(L) with Alzheimer or patients. ClinicalTrials.gov queries run the same day.

The search restricted to clinical trial or randomized controlled trial publication types returned 1 record, the 2007 phase 1 study. A PubMed search for FGLL or FGL(L) with Alzheimer or patients returned the same single record, so the Alzheimer patient studies that the 2007 authors said were being planned do not appear in PubMed 19 years later. A ClinicalTrials.gov query for NCAM mimetic peptide Alzheimer returned no studies, and a query for FGLL returned 2 studies, both unrelated (a pediatric cancer care platform and a children's spiritual diary study). The records reviewed contain no efficacy trial of FGL for any condition and no repeat-dose human safety data.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

How does FGL work?

FGL matches the NCAM binding site for fibroblast growth factor receptor 1. In rat hippocampal neurons it enhanced presynaptic function through FGFR1 activation, and in aged rats it restored hippocampal IGF-1 and lowered interferon-gamma.

FGL corresponds to the binding site of NCAM for fibroblast growth factor receptor 1. In primary cultures of hippocampal neurons it enhanced presynaptic function through activation of FGFR1 and promoted synapse formation.

In aged rats it reversed the age-related decline in hippocampal IGF-1 and abrogated the age-related increase in interferon-gamma. In primary neurons it promoted IGF-1 release, with IGF-1 pivotal in FGL induction of neuronal Akt phosphorylation and CD200 ligand expression.

In the 2019 comparison, cerebrospinal fluid levels of the FGLs correlated with blood plasma levels in rats and non-human primates. In the phase 1 study, plasma concentrations after intranasal FGL(L) were quantifiable at 100 and 200 mg and undetectable at 25 mg. No half-life is reported in the sources reviewed.

PubChem: FGL peptide identity, 15-mer

Chemical identity record

National Library of Medicine. PubChem compound record CID 16200289 (FGL peptide).

FGL peptide, the FG loop peptide, is a synthetic 15-amino-acid peptide corresponding to the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. PubChem lists it as CID 16200289, C71H116N20O25, molecular weight 1649.8, CAS 499993-62-3.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic 15-mer
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The PubChem record is for FGL peptide. The human data on this page are for FGL(L), and other studies used plannexin, FGLL and FGLS, so a record or result for one preparation does not automatically describe another.

Read the original source
Founding plasticity result: rats, injection into the brain ventricles, long-lasting memory improvement

Animal study

Cambon K et al. J Neurosci. 2004;24(17):4197-204. PMID 15115815.

Intracerebroventricular administration of FGL immediately after training rats in fear conditioning or water maze learning induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced presynaptic function through activation of FGFR1 and promoted synapse formation.

Participants / model
Rats; primary rat hippocampal neuron cultures
Treatment
Intracerebroventricular injection in vivo; media exposure in vitro
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the founding result for the plasticity claim, and it was produced by direct injection into the brain ventricles, not by a peripheral dose.

Read the original source
Aged rats: IGF-1 restored, interferon-gamma increase abrogated in hippocampus

Animal study

Downer EJ et al. J Neurochem. 2009;109(5):1516-25. PMID 19457161.

FGL reversed the age-related decline in hippocampal insulin-like growth factor-1 and abrogated the age-related increase in interferon-gamma, and it promoted IGF-1 release from primary neurons, with IGF-1 pivotal in FGL induction of neuronal Akt phosphorylation and CD200 ligand expression.

Participants / model
Aged rats; primary rat neurons
Treatment
FGL administration as dosed in the report; route not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is a hippocampal glial and cytokine result in aged rats, not an anti-inflammatory result in people.

Read the original source
2019 comparison: plannexin, FGLL and FGLS behave differently; CSF tracks plasma in rats and primates

Animal study

Turner CA et al. Neuropsychopharmacology. 2019;44(2):356-363. PMID 29703997.

A 2019 study tested the NCAM mimetics plannexin, FGLL and FGLS side by side and found different profiles for each. Plannexin acutely increased and chronically decreased anxiety with no antidepressant effect in rats; FGLL had acute anxiogenic effects and chronic antidepressant effects; FGLS had antidepressant effects without modulating anxiety-like behavior, and those effects were blocked by an AMPA receptor antagonist. Cisternal cerebrospinal fluid levels of the FGLs correlated with blood plasma levels in rats and non-human primates, and the CSF-to-blood ratios of FGLS were comparable in both species.

Participants / model
Rats and non-human primates
Treatment
Peripheral administration of NCAM peptide mimetics; CSF and plasma sampling
Follow-up
Acute and chronic dosing; durations not stated in the available record
Study design
Original preclinical study
Funding
not stated in the source

A product labeled FGL is not automatically the preparation that produced any given result. In PubMed the string FGL also indexes fibrinogen-like protein 1 and fibrinogen-like protein 2, which are unrelated molecules, so secondary sources citing FGL studies should be read against the molecule actually studied.

Read the original source
Phase 1: 24 healthy men, single intranasal doses, tolerability and plasma levels

Clinical trial

Anand R et al. Clin Pharmacokinet. 2007;46(4):351-8. PMID 17375985.

All three single intranasal doses were well tolerated, with no clinically notable abnormalities in ECG, vital signs or laboratory tests. Three subjects (13%) reported five adverse events: a transient burning sensation in the nose lasting under 3 minutes in two subjects at 200 mg, and runny eyes lasting under 2 minutes in one subject at 25 mg; one of those subjects also had dizziness, vomiting and headache starting more than 2 days after dosing, which was not judged related to the drug. Plasma concentrations were quantifiable up to 1 hour after the 100 mg dose and up to 4 hours after the 200 mg dose, and were undetectable at all timepoints at 25 mg. Mean Cmax was 0.52 ng/mL at 100 mg and 1.38 ng/mL at 200 mg; mean AUC(24) was 1.27 and 4.05 ng.h/mL.

Participants / model
24 healthy male volunteers (mean age 42, range 24 to 55)
Treatment
Single intranasal doses of FGL(L) of 25, 100 and 200 mg in sequential cohorts
Follow-up
8 days
Study design
Open-label phase 1 single ascending dose study
Funding
not stated in the source

This is a single-dose tolerability and pharmacokinetic study in healthy men. It measured no cognitive, protective or anti-inflammatory outcome. The doses are what the study gave, not an established or suggested amount.

Read the original source

What risks do the studies report?

In 24 healthy men, three reported five adverse events after single intranasal doses, all brief or judged unrelated, and there are no repeat-dose human safety data. In uninjured rats, FGL caused a 40% loss of CA1 pyramidal cells.

In the phase 1 study, three of 24 healthy men (13%) reported five adverse events: a transient burning sensation in the nose lasting under 3 minutes in two subjects at 200 mg, and runny eyes lasting under 2 minutes in one subject at 25 mg. One of those subjects also had dizziness, vomiting and headache starting more than 2 days after dosing, which was not judged related to the drug. There were no clinically notable abnormalities in ECG, vital signs or laboratory tests.

No repeat-dose human safety data exist, and no efficacy trial exists in any human population.

In young adult rats, FGL treatment without amyloid-beta caused a 40% decrease in CA1 pyramidal cells, the same size as the loss caused by the amyloid-beta insult that FGL partly alleviated. The authors concluded that FGL is potentially disruptive in non-pathological conditions while being neuroprotective in disease-like conditions.

Related preparations had different profiles in rats, so a result or an adverse event for one preparation does not describe another.

Phase 1: 24 healthy men, single intranasal doses, tolerability and plasma levels

Clinical trial

Anand R et al. Clin Pharmacokinet. 2007;46(4):351-8. PMID 17375985.

All three single intranasal doses were well tolerated, with no clinically notable abnormalities in ECG, vital signs or laboratory tests. Three subjects (13%) reported five adverse events: a transient burning sensation in the nose lasting under 3 minutes in two subjects at 200 mg, and runny eyes lasting under 2 minutes in one subject at 25 mg; one of those subjects also had dizziness, vomiting and headache starting more than 2 days after dosing, which was not judged related to the drug. Plasma concentrations were quantifiable up to 1 hour after the 100 mg dose and up to 4 hours after the 200 mg dose, and were undetectable at all timepoints at 25 mg. Mean Cmax was 0.52 ng/mL at 100 mg and 1.38 ng/mL at 200 mg; mean AUC(24) was 1.27 and 4.05 ng.h/mL.

Participants / model
24 healthy male volunteers (mean age 42, range 24 to 55)
Treatment
Single intranasal doses of FGL(L) of 25, 100 and 200 mg in sequential cohorts
Follow-up
8 days
Study design
Open-label phase 1 single ascending dose study
Funding
not stated in the source

This is a single-dose tolerability and pharmacokinetic study in healthy men. It measured no cognitive, protective or anti-inflammatory outcome. The doses are what the study gave, not an established or suggested amount.

Read the original source
Injured and uninjured young rats: protection after amyloid-beta, 40% CA1 loss without it

Animal study

Corbett NJ et al. PLoS One. 2013;8(8):e71479. PMID 23951173.

Young adult rats given amyloid-beta(25-35) into the right lateral ventricle showed impaired social recognition memory at 24 days, and this impairment was prevented by systemic FGL treatment. Amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 that FGL partially alleviated. However, FGL treatment without amyloid-beta also caused a 40% decrease in CA1 pyramidal cells. The authors concluded that FGL is potentially disruptive in non-pathological conditions while being neuroprotective in disease-like conditions.

Participants / model
Young adult rats, injured and uninjured
Treatment
Systemic FGL treatment; amyloid-beta(25-35) injected into the right lateral ventricle
Follow-up
Social recognition memory tested at 24 days
Study design
Original preclinical study with stereological cell counts
Funding
not stated in the source

This is the one study that tested uninjured animals, and it found cell loss rather than protection. That is the opposite of what a healthy user is buying.

Read the original source
2019 comparison: plannexin, FGLL and FGLS behave differently; CSF tracks plasma in rats and primates

Animal study

Turner CA et al. Neuropsychopharmacology. 2019;44(2):356-363. PMID 29703997.

A 2019 study tested the NCAM mimetics plannexin, FGLL and FGLS side by side and found different profiles for each. Plannexin acutely increased and chronically decreased anxiety with no antidepressant effect in rats; FGLL had acute anxiogenic effects and chronic antidepressant effects; FGLS had antidepressant effects without modulating anxiety-like behavior, and those effects were blocked by an AMPA receptor antagonist. Cisternal cerebrospinal fluid levels of the FGLs correlated with blood plasma levels in rats and non-human primates, and the CSF-to-blood ratios of FGLS were comparable in both species.

Participants / model
Rats and non-human primates
Treatment
Peripheral administration of NCAM peptide mimetics; CSF and plasma sampling
Follow-up
Acute and chronic dosing; durations not stated in the available record
Study design
Original preclinical study
Funding
not stated in the source

A product labeled FGL is not automatically the preparation that produced any given result. In PubMed the string FGL also indexes fibrinogen-like protein 1 and fibrinogen-like protein 2, which are unrelated molecules, so secondary sources citing FGL studies should be read against the molecule actually studied.

Read the original source
Searches, 9 October 2026: one clinical trial record, the phase 1 study; no efficacy trial

PubMed search record

PubMed search run on 9 October 2026: (FGL peptide OR FG loop peptide OR FGLL) restricted to clinical trial or randomized controlled trial publication types, 1 record. A second PubMed search for FGLL or FGL(L) with Alzheimer or patients. ClinicalTrials.gov queries run the same day.

The search restricted to clinical trial or randomized controlled trial publication types returned 1 record, the 2007 phase 1 study. A PubMed search for FGLL or FGL(L) with Alzheimer or patients returned the same single record, so the Alzheimer patient studies that the 2007 authors said were being planned do not appear in PubMed 19 years later. A ClinicalTrials.gov query for NCAM mimetic peptide Alzheimer returned no studies, and a query for FGLL returned 2 studies, both unrelated (a pediatric cancer care platform and a children's spiritual diary study). The records reviewed contain no efficacy trial of FGL for any condition and no repeat-dose human safety data.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

Why does FGL sit in C tier?

FGL has a defined 15-mer, a clear target, a substantial rat literature and one phase 1 study in healthy men, but no efficacy trial in any human population in 19 years, and uninjured rats lost CA1 pyramidal cells.

FGL has a defined 15-mer with a chemical record, a clear receptor target, a rat literature on memory, synaptic structure and glial activation, and an actual phase 1 study in 24 healthy men that found single intranasal doses up to 200 mg well tolerated with measurable plasma exposure.

What it lacks is a single efficacy trial in any human population in the 19 years since that phase 1, and the development program it was run for does not appear in the records reviewed to have continued. The rat data also contain a finding that cuts against the healthy-user case: FGL given to uninjured rats reduced CA1 pyramidal cells by 40%, the same size as the amyloid insult it partly alleviated.

PubChem: FGL peptide identity, 15-mer

Chemical identity record

National Library of Medicine. PubChem compound record CID 16200289 (FGL peptide).

FGL peptide, the FG loop peptide, is a synthetic 15-amino-acid peptide corresponding to the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. PubChem lists it as CID 16200289, C71H116N20O25, molecular weight 1649.8, CAS 499993-62-3.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic 15-mer
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The PubChem record is for FGL peptide. The human data on this page are for FGL(L), and other studies used plannexin, FGLL and FGLS, so a record or result for one preparation does not automatically describe another.

Read the original source
Phase 1: 24 healthy men, single intranasal doses, tolerability and plasma levels

Clinical trial

Anand R et al. Clin Pharmacokinet. 2007;46(4):351-8. PMID 17375985.

All three single intranasal doses were well tolerated, with no clinically notable abnormalities in ECG, vital signs or laboratory tests. Three subjects (13%) reported five adverse events: a transient burning sensation in the nose lasting under 3 minutes in two subjects at 200 mg, and runny eyes lasting under 2 minutes in one subject at 25 mg; one of those subjects also had dizziness, vomiting and headache starting more than 2 days after dosing, which was not judged related to the drug. Plasma concentrations were quantifiable up to 1 hour after the 100 mg dose and up to 4 hours after the 200 mg dose, and were undetectable at all timepoints at 25 mg. Mean Cmax was 0.52 ng/mL at 100 mg and 1.38 ng/mL at 200 mg; mean AUC(24) was 1.27 and 4.05 ng.h/mL.

Participants / model
24 healthy male volunteers (mean age 42, range 24 to 55)
Treatment
Single intranasal doses of FGL(L) of 25, 100 and 200 mg in sequential cohorts
Follow-up
8 days
Study design
Open-label phase 1 single ascending dose study
Funding
not stated in the source

This is a single-dose tolerability and pharmacokinetic study in healthy men. It measured no cognitive, protective or anti-inflammatory outcome. The doses are what the study gave, not an established or suggested amount.

Read the original source
Searches, 9 October 2026: one clinical trial record, the phase 1 study; no efficacy trial

PubMed search record

PubMed search run on 9 October 2026: (FGL peptide OR FG loop peptide OR FGLL) restricted to clinical trial or randomized controlled trial publication types, 1 record. A second PubMed search for FGLL or FGL(L) with Alzheimer or patients. ClinicalTrials.gov queries run the same day.

The search restricted to clinical trial or randomized controlled trial publication types returned 1 record, the 2007 phase 1 study. A PubMed search for FGLL or FGL(L) with Alzheimer or patients returned the same single record, so the Alzheimer patient studies that the 2007 authors said were being planned do not appear in PubMed 19 years later. A ClinicalTrials.gov query for NCAM mimetic peptide Alzheimer returned no studies, and a query for FGLL returned 2 studies, both unrelated (a pediatric cancer care platform and a children's spiritual diary study). The records reviewed contain no efficacy trial of FGL for any condition and no repeat-dose human safety data.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Injured and uninjured young rats: protection after amyloid-beta, 40% CA1 loss without it

Animal study

Corbett NJ et al. PLoS One. 2013;8(8):e71479. PMID 23951173.

Young adult rats given amyloid-beta(25-35) into the right lateral ventricle showed impaired social recognition memory at 24 days, and this impairment was prevented by systemic FGL treatment. Amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 that FGL partially alleviated. However, FGL treatment without amyloid-beta also caused a 40% decrease in CA1 pyramidal cells. The authors concluded that FGL is potentially disruptive in non-pathological conditions while being neuroprotective in disease-like conditions.

Participants / model
Young adult rats, injured and uninjured
Treatment
Systemic FGL treatment; amyloid-beta(25-35) injected into the right lateral ventricle
Follow-up
Social recognition memory tested at 24 days
Study design
Original preclinical study with stereological cell counts
Funding
not stated in the source

This is the one study that tested uninjured animals, and it found cell loss rather than protection. That is the opposite of what a healthy user is buying.

Read the original source

Studies and sources

PubChem: FGL peptide identity, 15-mer

Chemical identity record

National Library of Medicine. PubChem compound record CID 16200289 (FGL peptide).

FGL peptide, the FG loop peptide, is a synthetic 15-amino-acid peptide corresponding to the binding site of the neural cell adhesion molecule (NCAM) for fibroblast growth factor receptor 1. PubChem lists it as CID 16200289, C71H116N20O25, molecular weight 1649.8, CAS 499993-62-3.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic 15-mer
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The PubChem record is for FGL peptide. The human data on this page are for FGL(L), and other studies used plannexin, FGLL and FGLS, so a record or result for one preparation does not automatically describe another.

Read the original source
2019 comparison: plannexin, FGLL and FGLS behave differently; CSF tracks plasma in rats and primates

Animal study

Turner CA et al. Neuropsychopharmacology. 2019;44(2):356-363. PMID 29703997.

A 2019 study tested the NCAM mimetics plannexin, FGLL and FGLS side by side and found different profiles for each. Plannexin acutely increased and chronically decreased anxiety with no antidepressant effect in rats; FGLL had acute anxiogenic effects and chronic antidepressant effects; FGLS had antidepressant effects without modulating anxiety-like behavior, and those effects were blocked by an AMPA receptor antagonist. Cisternal cerebrospinal fluid levels of the FGLs correlated with blood plasma levels in rats and non-human primates, and the CSF-to-blood ratios of FGLS were comparable in both species.

Participants / model
Rats and non-human primates
Treatment
Peripheral administration of NCAM peptide mimetics; CSF and plasma sampling
Follow-up
Acute and chronic dosing; durations not stated in the available record
Study design
Original preclinical study
Funding
not stated in the source

A product labeled FGL is not automatically the preparation that produced any given result. In PubMed the string FGL also indexes fibrinogen-like protein 1 and fibrinogen-like protein 2, which are unrelated molecules, so secondary sources citing FGL studies should be read against the molecule actually studied.

Read the original source
Founding plasticity result: rats, injection into the brain ventricles, long-lasting memory improvement

Animal study

Cambon K et al. J Neurosci. 2004;24(17):4197-204. PMID 15115815.

Intracerebroventricular administration of FGL immediately after training rats in fear conditioning or water maze learning induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced presynaptic function through activation of FGFR1 and promoted synapse formation.

Participants / model
Rats; primary rat hippocampal neuron cultures
Treatment
Intracerebroventricular injection in vivo; media exposure in vitro
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the founding result for the plasticity claim, and it was produced by direct injection into the brain ventricles, not by a peripheral dose.

Read the original source
Aged rats: IGF-1 restored, interferon-gamma increase abrogated in hippocampus

Animal study

Downer EJ et al. J Neurochem. 2009;109(5):1516-25. PMID 19457161.

FGL reversed the age-related decline in hippocampal insulin-like growth factor-1 and abrogated the age-related increase in interferon-gamma, and it promoted IGF-1 release from primary neurons, with IGF-1 pivotal in FGL induction of neuronal Akt phosphorylation and CD200 ligand expression.

Participants / model
Aged rats; primary rat neurons
Treatment
FGL administration as dosed in the report; route not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is a hippocampal glial and cytokine result in aged rats, not an anti-inflammatory result in people.

Read the original source
Injured and uninjured young rats: protection after amyloid-beta, 40% CA1 loss without it

Animal study

Corbett NJ et al. PLoS One. 2013;8(8):e71479. PMID 23951173.

Young adult rats given amyloid-beta(25-35) into the right lateral ventricle showed impaired social recognition memory at 24 days, and this impairment was prevented by systemic FGL treatment. Amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 that FGL partially alleviated. However, FGL treatment without amyloid-beta also caused a 40% decrease in CA1 pyramidal cells. The authors concluded that FGL is potentially disruptive in non-pathological conditions while being neuroprotective in disease-like conditions.

Participants / model
Young adult rats, injured and uninjured
Treatment
Systemic FGL treatment; amyloid-beta(25-35) injected into the right lateral ventricle
Follow-up
Social recognition memory tested at 24 days
Study design
Original preclinical study with stereological cell counts
Funding
not stated in the source

This is the one study that tested uninjured animals, and it found cell loss rather than protection. That is the opposite of what a healthy user is buying.

Read the original source
Phase 1: 24 healthy men, single intranasal doses, tolerability and plasma levels

Clinical trial

Anand R et al. Clin Pharmacokinet. 2007;46(4):351-8. PMID 17375985.

All three single intranasal doses were well tolerated, with no clinically notable abnormalities in ECG, vital signs or laboratory tests. Three subjects (13%) reported five adverse events: a transient burning sensation in the nose lasting under 3 minutes in two subjects at 200 mg, and runny eyes lasting under 2 minutes in one subject at 25 mg; one of those subjects also had dizziness, vomiting and headache starting more than 2 days after dosing, which was not judged related to the drug. Plasma concentrations were quantifiable up to 1 hour after the 100 mg dose and up to 4 hours after the 200 mg dose, and were undetectable at all timepoints at 25 mg. Mean Cmax was 0.52 ng/mL at 100 mg and 1.38 ng/mL at 200 mg; mean AUC(24) was 1.27 and 4.05 ng.h/mL.

Participants / model
24 healthy male volunteers (mean age 42, range 24 to 55)
Treatment
Single intranasal doses of FGL(L) of 25, 100 and 200 mg in sequential cohorts
Follow-up
8 days
Study design
Open-label phase 1 single ascending dose study
Funding
not stated in the source

This is a single-dose tolerability and pharmacokinetic study in healthy men. It measured no cognitive, protective or anti-inflammatory outcome. The doses are what the study gave, not an established or suggested amount.

Read the original source

Why is FGL peptide in C tier?

C fits a defined peptide with a substantial rat literature, one phase 1 tolerability study and no efficacy trial. The rat work supports memory and synaptic effects after injection into the brain ventricles and protection in injury models, but uninjured rats lost CA1 pyramidal cells, and no person has been tested for any cognitive, protective or anti-inflammatory outcome in the 19 years since the phase 1.