hot sale Dihexa Neuroprotective Nootropic Peptide

Product Description

Dihexa (CAS No. 1401708-83-5, development code PNB-0408) is a synthetic oligopeptide compound developed by a research team at Washington State University based on structural modifications of angiotensin IV, with the sequence Hexanoyl-Tyr-Ile-Ahx-NH2. Through chemical modification, it eliminates the sites in the natural peptide that are susceptible to enzymatic degradation, thereby achieving excellent metabolic stability and a long in vivo half-life. It also possesses oral bioavailability and the ability to cross the blood-brain barrier, addressing the challenges faced by natural peptide drugs, such as difficulty in reaching the central nervous system and an excessively short half-life.

In terms of its mechanism of action, Dihexa binds to hepatocyte growth factor (HGF) with extremely high affinity (Kd = 65 pM) and enhances the signaling activity of its receptor, c-Met, thereby activating signaling pathways such as PI3K/AKT and MAPK/ERK that are closely associated with neuronal survival, dendritic growth, and synapse formation. In in vitro cultured hippocampal neurons, Dihexa at picomolar concentrations can significantly promote dendritic spine formation and synapse formation—its efficacy under this specific metric is approximately seven orders of magnitude higher than that of brain-derived neurotrophic factor (BDNF), which is the primary reason for the intense attention it has received in the field of neuroscience.

Key Benefits

Dihexa’s core efficacy revolves around “promoting neural connections.” Rather than directly activating receptors, it binds to HGF and allosterically enhances signaling in the HGF/c-Met pathway, thereby promoting the formation of neuronal dendritic spines and synapses at extremely low concentrations—the physiological basis of learning and memory. In animal models, Dihexa has demonstrated clear cognitive-enhancing activity: it can reverse drug-induced spatial learning impairments, improve learning performance in aged rats, and enhance memory behavior while reducing neuroinflammation in transgenic mice with Alzheimer’s disease. Additionally, some studies suggest it has potential for neuroprotection and the protection of auditory hair cells. Specifically:

1. Promotes synapse and dendritic spine formation: In vitro experiments show that at picomolar concentrations, it significantly increases the number of dendritic spines in hippocampal neurons and promotes synaptic connection formation; at this concentration, its potency is approximately 10⁷ times that of BDNF (based on specific in vitro experimental parameters).

2. Enhancement of the HGF/c-Met signaling pathway: It binds to HGF with high affinity (Kd = 65 pM), allosterically enhances c-Met activation, and mediates neuroprotective and plasticity-related signaling pathways such as PI3K/AKT and MAPK/ERK.

3. Improves learning and memory: In animal studies, it reverses scopolamine-induced spatial learning deficits and improves learning performance in the water maze in aged rats.

4. Neuroprotective and anti-inflammatory effects: In APP/PS1 Alzheimer’s disease model mice, it improves memory parameters, increases synaptophysin expression, and reduces glial cell activation as well as levels of inflammatory factors such as IL-1β and TNF-α.

5. Protection of auditory hair cells (research stage): In a zebrafish model, it provides dose-dependent protection of lateral line hair cells against damage caused by aminoglycoside antibiotics.

Applications

Dihexa is primarily used in basic neuroscience research and drug development, serving as a key molecular tool for researchers studying synaptic plasticity, cognitive mechanisms, and the pathology of neurodegenerative diseases. Its oral bioavailability and ability to cross the blood-brain barrier also make it a model compound for evaluating peptide drug modification strategies (stability, bioavailability, and brain-targeted delivery). Current applications are concentrated in the preclinical research domain and primarily include:

1. Cognitive and synaptic plasticity research: Used in in vitro and animal models to investigate the molecular mechanisms of learning and memory, as well as dendritic spine dynamics and synaptogenesis.

2. Alzheimer’s disease and neurodegenerative disease research: As a modulator of the HGF/c-Met pathway, it is used for cognitive intervention and pathological mechanism studies in AD and aging models.

3. Brain injury and neural repair research: Exploring the potential to promote neural connection repair in scenarios such as traumatic brain injury and perioperative brain protection.

4. Drug screening and lead compound optimization: Serving as a positive reference tool for the HGF/c-Met pathway, used in the design and activity evaluation of similar neuroactive peptides.

5. Peptide Delivery and Stability Studies: As a model compound, it is used to investigate strategies for improving peptide bioavailability, prolonging half-life, and enabling targeted delivery to the brain.

6. Development of Analytical Assay Methods: As a reference standard with a well-defined structure and stable activity, it is used for the calibration and validation of peptide detection methods such as chromatography and mass spectrometry.