Evidence Grade C — Moderate human evidence. 256 published studies, 92 human. 0 registered clinical trials.
Medically reviewed by a licensed medical professional
FGL is a 15-amino-acid peptide derived from a brain adhesion protein (NCAM), designed to mimic a specific growth factor interaction involved in learning and memory. A Phase I trial in healthy volunteers demonstrated that intranasal delivery was well tolerated. It has no marketing authorisation.
FGL is also known by these brand and alternate names:
256 published studies: 92 human, 89 animal, 27 in-vitro, 15 reviews
FGL has no marketing authorisation. A Phase I trial (24 healthy volunteers) of intranasal FGL demonstrated tolerability with only mild adverse events. Preclinical studies reported effects on memory in animal models.
The compound has progressed further through formal development than many research peptides, having completed a Phase I safety study. However, no efficacy trials have been conducted in patients, and clinical development beyond Phase I has not been reported.
Research suggests FGL mimics a natural protein-protein interaction between NCAM and the FGFR1 growth factor receptor, potentially activating downstream signalling pathways involved in neuronal survival and plasticity. These proposed mechanisms are based on cell culture and animal studies.
Research suggests multiple independent research groups (in Copenhagen, Madrid, Dublin, and Lausanne) have contributed studies, providing better cross-validation than most compounds at this stage. The completed Phase I trial (24 subjects) with a favourable safety profile is a meaningful milestone. However, no human efficacy data exist, and one animal study raised concerns about potentially lowering the seizure threshold — a safety question for people prone to epilepsy. The development company appears to be inactive, making the compound's clinical future uncertain. The long-term consequences of chronically activating the FGFR1 growth factor receptor — the compound's proposed mechanism — are not well understood.
PeptideTrace tracks 0 registered clinical trials for FGL sourced from ClinicalTrials.gov.
No trials registered on ClinicalTrials.gov for this compound.
FGL (FG Loop peptide) is a 15-amino-acid peptide derived from the FG loop of the neural cell adhesion molecule (NCAM) second fibronectin type III module, corresponding to the NCAM-FGFR1 binding interface. Its sequence is EVYVVAENQQGKSKA, with molecular weight approximately 1,649.8 g/mol for the monomer (CAS: 499993-62-3; PubChem CID: 16200289). The dimeric form FGL(L) was selected for clinical development because the monomer is much less efficient at activating FGFR. A tetrameric form FGL(d) also exists. In a Phase I study, intranasal FGL(L) at 200 mg showed Cmax of 1.38 ng/mL and AUC24 of 4.05 ng*h/mL. In rats, subcutaneous FGL reached CSF within 10 minutes with stable concentrations for up to 5 hours. Developed by Enkam Pharmaceuticals (Copenhagen). Not approved by any regulatory agency.
FGL mimics NCAM's heterophilic interaction with FGFR1, inducing a 2-fold increase in FGFR1 phosphorylation (confirmed blocked by FGFR1 inhibitor SU5402). Downstream cascades include PLCgamma phosphorylation, MAPK/ERK activation, PI3K/Akt survival signaling, and PKC activation, which is the critical mediator. Research suggests PKC activation facilitates synaptic delivery of AMPA receptors, producing long-lasting potentiation of synaptic transmission. LTP nearly doubled in FGL-treated hippocampal slices. PKC inhibition abolishes all FGL-mediated cognitive enhancement. Research suggests potent anti-inflammatory effects: FGL attenuates age-related microglial activation, reduces pro-inflammatory IL-1beta, enhances IL-4 release from glia, and increases neuronal CD200 expression (an anti-inflammatory signal), restoring age-related LTP impairment.
A Phase I clinical trial (Anand et al., 2007; N=24 healthy volunteers) demonstrated that intranasal FGL(L) at 25, 100, and 200 mg was well tolerated with no clinically significant abnormalities. Only 3 of 24 subjects reported 5 mild adverse events (transient nasal burning, runny eyes). Preclinical studies include Cambon et al. (2004, J. Neuroscience), showing ICV FGL immediately after training produced long-lasting memory improvement in rats (fear conditioning and Morris water maze). Knafo et al. (2012, PLoS Biology) demonstrated FGL facilitated AMPA receptor synaptic delivery, nearly doubling LTP, with PKC inhibitor abolishing the effect. Klementiev et al. (2007) showed FGL prevented amyloid-beta-induced neuropathology and memory impairment in rats. Enkam Pharmaceuticals planned a Phase I/II trial in 48 early-stage Alzheimer's patients but development appears stalled or discontinued. No efficacy data in humans exists.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
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P21 has no marketing authorisation. No human clinical trials have been conducted. The evidence base consists entirely of studies in transgenic Alzheimer's disease mouse models, conducted primarily by a single research group. Animal studies reported behavioural and biochemical changes in AD mouse models following chronic oral administration. The translation of results from transgenic mouse models of Alzheimer's disease to human disease has historically been extremely poor — the vast majority of compounds showing efficacy in such models have failed in human trials. Products available through unregulated channels lack pharmaceutical quality assurance.
Semax is approved in Russia for stroke recovery and cognitive conditions. It has not been approved by the FDA, EMA, or other major Western regulatory agencies, and the clinical evidence base has not undergone Western regulatory review. Published clinical studies are predominantly Russian. The largest published study (110 stroke patients) reported correlations between treatment and BDNF levels. The evidence does not meet the standards typically required for FDA or EMA approval. Its regulatory status is limited to Russia and certain former Soviet states.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
