Dihexa vs FGL Peptide
Both Dihexa and FGL Peptide are engineered synaptogenic research peptides. Both drive dendritic spine formation and increase synapse density in hippocampal preparations, both are studied in cognitive-ageing and Alzheimer's-model research, and both share theoretical safety concerns around exogenous receptor-tyrosine-kinase agonism. But they target different receptor axes and have very different practical profiles — most importantly, Dihexa is orally active and FGL is not.
At a glance
| Dihexa | FGL Peptide | |
|---|---|---|
| Molecular target | HGF / c-Met receptor axis | NCAM / FGFR1 receptor axis |
| Molecular size | Hexapeptide (~520 Da) | 15-mer (~1.6 kDa) |
| Structural origin | Angiotensin-IV C-terminal fragment | NCAM F3-2 domain FGL loop |
| Oral bioavailability | Yes (engineered oral activity) | No — parenteral only |
| Primary route in research | Oral (propylene-glycol vehicle) | Subcutaneous |
| Signature effect | Picomolar-concentration dendritic spinogenesis | Neurite outgrowth + adult hippocampal neurogenesis |
| Neurogenic component | Primarily synaptogenic (existing neurons) | Both synaptogenic and neurogenic (new neurons) |
| Human trials | None registered | Early Alzheimer's evaluation (did not progress to Phase III) |
| Evidence tier | C (preclinical only, strong) | B (early clinical + strong preclinical) |
| Theoretical oncogenic concern | c-Met activation in tumour biology | FGFR1 activation in tumour biology |
| UK status | Research chemical | Research chemical |
Different receptors, converging downstream
Mechanistic differences and similarities
Dihexa activates the c-Met receptor — the cognate receptor for hepatocyte growth factor (HGF). c-Met signalling drives dendritic spine formation and synaptic remodelling. Dihexa acts partly by directly binding c-Met and partly by stabilising endogenous HGF dimers, prolonging the endogenous signalling.
FGL activates FGFR1 — the cognate receptor for fibroblast growth factor. FGFR1 signalling drives neurite outgrowth, synaptogenesis, and adult neurogenesis. FGL reproduces the FGL loop of NCAM (neural cell adhesion molecule), which is the natural FGFR1 ligand in trans-synaptic signalling.
Both receptor systems converge downstream on the same signalling cascades — PI3K-Akt, MAPK/ERK, PLCγ — that stabilise activity-dependent synapses and drive the synaptogenic effect. This is why the two peptides produce broadly similar cellular-level and behavioural-level cognitive effects despite acting on different upstream receptors.
The neurogenic component differs: FGL has a stronger reported effect on adult hippocampal neurogenesis (new neurons in the dentate gyrus) than Dihexa. Dihexa's flagship finding is spinogenic (new spines on existing neurons) rather than neurogenic. For research designs where making new neurons matters, FGL has the stronger evidence.
Practical selection