FGL Peptide

FGL (FG Loop peptide; Glu-Val-Tyr-Val-Val-Ala-Glu-Asn-Gln-Gln-Gly-Lys-Ser-Lys-Ala; sometimes called the FGL peptide or NCAM-derived FGFR agonist; molecular weight approximately 1622 Da) is a synthetic 15-residue peptide modeled on the second fibronectin type III repeat (FnIII) domain of neural cell adhesion molecule (NCAM), specifically the Phe-Gly loop responsible for fibroblast growth factor receptor 1 (FGFR1) interaction. NCAM is a transmembrane glycoprotein expressed at high levels in developing and adult nervous system tissue that mediates cell-cell adhesion through homophilic NCAM-NCAM binding and signals across the membrane through cis-binding to FGFR1. The FGL peptide was designed at the University of Copenhagen by Elisabeth Bock and Vladimir Berezin as a small-molecule mimetic of the NCAM-FGFR interaction, capable of activating FGFR1 signaling without the broad effects of full NCAM ectodomain or full-length FGF ligands. Reported activities include neurite outgrowth promotion in primary cortical and hippocampal neurons, protection against glutamate excitotoxicity, anxiolysis and pro-cognitive effects in rodent fear conditioning and Morris water maze paradigms, and recovery promotion in models of traumatic brain injury and stroke. Routes studied include subcutaneous, intraperitoneal, and intranasal administration. Plasma half-life is short (approximately 30 minutes); the central nervous system exposure after intranasal administration is substantially higher than after parenteral routes, owing to direct olfactory and trigeminal pathway transport. The compound advanced through ENKAM Pharmaceuticals (a University of Copenhagen spin-out) into early clinical development for Alzheimer's disease and cognitive impairment in the late 2000s; clinical development has not produced a marketed agent. The principal limitation on the strength of the evidence is the dominance of the originating laboratory's publications and the absence of independent replication of key behavioral findings.