GK-2

GK-2 (hexamethylenediamide bis-(N-monosuccinyl-L-glutamyl-L-lysine)) is a small dimeric dipeptide designed to mimic nerve growth factor (NGF) rather than replace it wholesale. It was rationally derived from the Asp93-Glu94-Lys95-Gln96 β-turn of NGF's fourth loop, with the central Glu-Lys dipeptide fragment forming the active pharmacophore, dimerized through a hexamethylenediamine linker with succinyl end caps.

It was developed at the V.V. Zakusov Research Institute of Pharmacology (Russian Academy of Medical Sciences) by the Gudasheva/Seredenin research group, the same team responsible for the related BDNF-mimetic compound GSB-106. GK-2 has been studied exclusively in preclinical (animal) models — there is no published human trial data, and it should be understood strictly as a research compound at this stage, not an established or dosed therapeutic.

Across rodent studies, GK-2 has shown neuroprotective effects in models of Alzheimer's-like cognitive deficit, Parkinson's disease, ischemic and hemorrhagic stroke, global cerebral ischemia, and traumatic brain injury, along with effects on pancreatic beta-cell survival in a diabetes model and a reported hypocoagulant effect.

// SELECTIVE TrkA AGONISM

GK-2 selectively engages the TrkA receptor rather than p75 — demonstrated directly in a 2023 study using TrkA-knockout versus TrkB-knockout cell lines, which showed GK-2's effects depend specifically on TrkA. This contrasts with full-length NGF, which can also engage p75.

// PI3K/AKT-DEPENDENT, MAPK-INDEPENDENT SIGNALING

GK-2 drives TrkA phosphorylation and downstream Akt activation, but notably does not increase Erk/MAPK phosphorylation the way native NGF does. Its neuroprotective effects are blocked by the PI3K inhibitor LY294002 but not by MAPK pathway inhibitors — a genuine mechanistic divergence from full NGF signaling, not an assumption drawn by analogy.

// NEUROPROTECTION ACROSS INJURY MODELS

In rodent models, GK-2 has improved outcomes in Alzheimer's-like cognitive deficit, Parkinson's disease, ischemic and hemorrhagic stroke, global cerebral ischemia, and traumatic brain injury — including improved motor function, reduced neuronal death, and stimulated neurite outgrowth in various models.

No human trial data exists for GK-2 — every study identified is preclinical, in rats or mice. This should not be presented as a clinically studied or dosed compound.

A vendor-sourced estimate placed molecular weight around 835 Da, but this could not be independently confirmed against a primary peer-reviewed source or a formula-bearing reference (e.g., PubChem) — it is therefore omitted from the structured molecular data above rather than stated as fact.

Reported preclinical effects: neuroprotection at nanomolar concentrations in vitro; cognitive restoration in an Alzheimer's-like rat model; efficacy in Parkinson's, stroke, and traumatic brain injury rodent models; pancreatic beta-cell survival benefit in a diabetes model; a reported hypocoagulant effect. All preclinical/animal-model findings — none have been tested in humans.