Dihexa

Cas：1401708-83-5

Product Information：

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

Synonym:

PNB-0408

PNB 0408

PNB0408

Dihexa

N-hexanoic-Tyr-Ile-(6) aminohexanoic amide

N-(1-Oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-L-isoleucinamide

Chemical Name: 

6-[(2S,3S)-2-[(2S)-2-hexanamido-3-(4-hydroxyphenyl)propanamido]-3-methylpentanamido]hexanamide

InChi Key:

XEUVNVNAVKZSPT-JTJYXVOQSA-N

InChi Code:

InChI=1S/C27H44N4O5/c1-4-6-8-12-24(34)30-22(18-20-13-15-21(32)16-14-20)26(35)31-25(19(3)5-2)27(36)29-17-10-7-9-11-23(28)33/h13-16,19,22,25,32H,4-12,17-18H2,1-3H3,(H2,28,33)(H,29,36)(H,30,34)(H,31,35)/t19-,22-,25-/m0/s1

Smiles Code:

O=C(N)CCCCCNC([C@@H](NC([C@@H](NC(CCCCC)=O)CC1=CC=C(O)C=C1)=O)[C@@H](C)CC)=O

Technical Data：

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

In Vitro:

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.

In Vivo:

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.

References：

1. Mathapati S, Siller R, Impellizzeri AA, Lycke M, Vegheim K, Almaas R, Sullivan GJ. Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells. Curr Protoc Stem Cell Biol. 2016 Aug 17;38:1G.6.1-1G.6.18. doi: 10.1002/cpsc.13. PubMed PMID: 27532814.

2. 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.

3. 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.

4. 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.

5. 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.

Products are for research use only. Not for human use.