Dihexa is a blood-brain barrier-permeable angiotensin IV analog which exhibits high affinity to HGF with Kd value of 65pM and induces c-Met phosphorylation in the presence of subthreshold concentrations of HGF and augment HGF-dependent cell scattering.
Dihexa (acetate), an oligopeptide drug, is an orally active and blood-brain barrier-permeable angiotensin IV analog. Dihexa binds to hepatocyte growth factor (HGF) with high affinity (Kd=65 pM) and potentiates its activity at its receptor, c-Met. Dihexa binds with high affinity to HGF and both dihexa and its parent compound Norleucine 1-AngIV induce c-Met phosphorylation in the presence of subthreshold concentrations of HGF and augment HGF-dependent cell scattering. Dihexa effectively inhibits HGF dimerization at 1 μM. While dihexa at 1 nM and 10 pM alone does not activate c-Met, it markedly augments the capacity of HGF at 1.25 and 2.5 ng/mL to activate c-Met[1]. Dihexa exhibits procognitive activity may have therapeutic potential as a treatment of Alzheimer’s disease. Dihexa reverses scopolamine-dependent spatial learning deficits. It improves spatial learning in aged rats. Dihexa induces spinogenesis in cultured hippocampal neurons[2]. A Dihexa concentration of 1 μM confers optimal protection from acute treatment with either ototoxin. Pretreatment with Dihexa does not affect the amount of fluorescently tagged gentamicin that enters hair cells, indicating that Dihexa's protection is likely mediated by intracellular events and not by inhibiting aminoglycoside entry[3].
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