Dihexa

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.

Product information

CAS Number: 1401708-83-5

Molecular Weight: 504.66

Formula: C27H44N4O5

Synonym:

PNB-0408

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

PNB 0408

PNB0408

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

Dihexa

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

Smiles: C[C@@H](CC)[C@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)CCCCC)C(=O)NCCCCCC(N)=O

InChiKey: XEUVNVNAVKZSPT-JTJYXVOQSA-N

InChi: 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

Technical Data

Appearance: White to Off-White Solid

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO (Slightly), Methanol (Slightly)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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.
6. 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.