Dihexa, also known as PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, is an oligopeptide drug derived from angiotensin IV that binds with high affinity to hepatocyte growth factor (HGF) and potentiates its activity at its receptor, c-Met. Dihexa has been found to potently improve cognitive function in animal models of Alzheimer's disease-like mental impairment. In an assay of neurotrophic activity, Dihexa was found to be seven orders of magnitude more potent than brain-derived neurotrophic factor.
Chemical Formula: C27H44N4O5
Exact Mass: 504.3312
Molecular Weight: 504.672
Elemental Analysis: C, 64.26; H, 8.79; N, 11.10; O, 15.85
N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
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. Further, dihexa and Nle1-AngIV induce hippocampal spinogenesis and synaptogenesis similar to HGF itself. 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.
Dihexa has a long circulating half-life. Dihexa exhibits procognitive activity. Dihexa reverses scopolamine-dependent spatial learning deficits. It improves spatial learning in aged rats. Dihexa induces spinogenesis in cultured hippocampal neurons.
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Siller R, Greenhough S, Naumovska E, Sullivan GJ. Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells. Stem Cell Reports. 2015 May 12;4(5):939-52. doi: 10.1016/j.stemcr.2015.04.001. PubMed PMID: 25937370; PubMed Central PMCID: PMC4437467.
Uribe PM, Kawas LH, Harding JW, Coffin AB. Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure. Front Cell Neurosci. 2015 Jan 28;9:3. doi: 10.3389/fncel.2015.00003. PubMed PMID: 25674052; PubMed Central PMCID: PMC4309183.
Wright JW, Harding JW. The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease. J Alzheimers Dis. 2015;45(4):985-1000. doi: 10.3233/JAD-142814. Review. PubMed PMID: 25649658.
Wright JW, Kawas LH, Harding JW. The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases. Prog Neurobiol. 2015 Feb;125:26-46. doi: 10.1016/j.pneurobio.2014.11.004. Review. PubMed PMID: 25455861.
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