Dihexa

Dihexa

Systematic (IUPAC) name
6-{2-[2-hexanamido-3-(4-hydroxyphenyl)propanamido]-3-methylpentanamido}hexanamide
Identifiers
CAS Number	1401708-83-5
PubChem	CID 162064814
Chemical data
Formula	C27H44N4O5
Molar mass	504.67 g·mol^−1
SMILES C(CCCCC)(=O)NC(C(=O)NC(C(=O)NCCCCCC(=O)N)C(CC)C)CC1=CC=C(C=C1)O
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) Key:XEUVNVNAVKZSPT-UHFFFAOYSA-N

Dihexa, also known as N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, is an oligopeptide and angiotensin IV-derived drug that binds with high affinity to hepatocyte growth factor (HGF) and potentiates its activity at its receptor, c-Met. Dihexa dramatically improves cognitive function in animal models of Alzheimer's disease-like mental impairment.^{[1][2][3][4][5][6][7][8][9][10]} In an assay of neurotrophic activity, Dihexa was found to be seven orders of magnitude more potent than brain-derived neurotrophic factor.^[11]

References

1. Joseph W. Harding, John W. Wright, Caroline C. Benoist, Leen H. Kawas, Gary A. Wayman (3 December 2013). "Patent US 8598118 - Hepatocyte growth factor mimics as therapeutic agents". Retrieved 11 October 2015.
2. Alene T McCoy, Caroline C Benoist, John W Wright, Leen H Kawas, Jyote Bule-Ghogare, Mingyan Zhu, Suzanne M Appleyard, Gary A Wayman, Joseph W Harding (October 2012). "Evaluation of metabolically stabilized angiotensin IV analogs as pro-cognitive/anti-dementia agents". The Journal of Pharmacology and Experimental Therapeutics 344: 141–54. doi:10.1124/jpet.112.199497. PMC 3533412. PMID 23055539.
3. Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA, Harding JW (November 2014). "The Procognitive and Synaptogenic Effects of Angiotensin IV–Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System". The Journal of Pharmacology And Experiemental Thereapeutics 351 (2): 390–402. doi:10.1124/jpet.114.218735. PMID 25187433.
4. Caroline C. Benoist, John W. Wright, Mingyan Zhu, Suzanne M. Appleyard, Gary A. Wayman, Joseph W. Harding (October 2011). "Facilitation of Hippocampal Synaptogenesis and Spatial Memory by C-Terminal Truncated Nle1-Angiotensin IV Analogs". The Journal of Pharmacology And Experiemental Thereapeutics 339 (1): 35–44. doi:10.1124/jpet.111.182220. PMC 3186286. PMID 21719467.
5. Phillip M. Uribe,Leen H. Kawas, Joseph W. Harding, Allison B. Coffin (January 2015). "Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure". Frontiers in Cellular Neuroscience 9: 3. doi:10.3389/fncel.2015.00003. PMC 4309183. PMID 25674052.
6. John W Wright, Joseph W. Harding (January 2015). "The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease". Journal of Alzheimer's Disease 45 (4): 985–1000. doi:10.3233/JAD-142814. PMID 25649658.
7. Richard Siller, Sebastian Greenhough, Elena Naumovska, Gareth J. Sullivan (May 2015). "Small-Molecule-Driven Hepatocyte Differentiation of Human Pluripotent Stem Cells". Stem Cell Reports 4 (5): 939–952. doi:10.1016/j.stemcr.2015.04.001. PMC 4437467. PMID 25937370.
8. "32. The Innovators: Designing Medicine's Holy Grail". KOMO News. 27 August 2015. Retrieved 11 October 2015.
9. "Brain Connections in Alzheimer's Rebuilt with New Peptide". GEN News Highlights. 11 October 2015. Retrieved 11 October 2015.
10. "Brain-Enhancing 'Smart Drugs' Are Going Commercial". VICE. 17 July 2014. Retrieved 11 October 2015.
11. "Prospective Alzheimer's drug builds new brain cell connections, improves cognitive function of rats". ScienceDaily. 11 October 2012. Retrieved 11 October 2015.