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Dihexa

Clinical data
Other names	N-(1-Oxohexyl)-l-tyrosyl-N-(6-amino-6-oxohexyl)-l-isoleucinamide
Identifiers
IUPAC name 6--3-methylpentanamido]hexanamide
CAS Number	1401708-83-5
PubChem CID	129010512
ChemSpider	57582587
UNII	9WYX65A5C2
Chemical and physical data
Formula	C27H44N4O5
Molar mass	504.672 g·mol
3D model (JSmol)	Interactive image
SMILES CCCCCC(=O)N(Cc1ccc(O)cc1)C(=O)N((C)CC)C(=O)NCCCCCC(N)=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)/t19-,22-,25-/m0/s1 Key:XEUVNVNAVKZSPT-JTJYXVOQSA-N

Dihexa (developmental code PNB-0408; also known as 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. The compound 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.

According to a patent, "Short duration safety studies with dihexa have uncovered no apparent toxicity. Of particular note is a lack of neoplastic induction, since c-Met is recognized as an oncogene. This is unsurprising since oncogenesis requires multiple mutations including both oncogene induction and tumor suppressor attenuation."

History

Dihexa was developed by Joseph Harding and his team at Washington State University. Later developments were done by M3 Biotechnology, a company founded to commercialize dihexa.

Fosgonimeton, a phosphate pro-drug of dihexa is currently in clinical trials for the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's disease

References

1. US 8598118, Harding JW, Wright JW, Benoist CC, Kawas LH, Wayman GA, "Hepatocyte growth factor mimics as therapeutic agents" 
2. Benoist CC, Wright JW, Zhu M, Appleyard SM, Wayman GA, Harding JW (October 2011). "Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs". The Journal of Pharmacology and Experimental Therapeutics. 339 (1): 35–44. doi:10.1124/jpet.111.182220. PMC 3186286. PMID 21719467.
3. Uribe PM, Kawas LH, Harding JW, Coffin AB (January 2015). "Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure". Frontiers in Cellular Neuroscience. 9 (3): 3. doi:10.3389/fncel.2015.00003. PMC 4309183. PMID 25674052.
4. Wright JW, Harding JW (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.
5. Siller R, Greenhough S, Naumovska E, Sullivan GJ (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.
6. "32. The Innovators: Designing Medicine's Holy Grail". KOMO News. 27 August 2015. Retrieved 11 October 2015.
7. "Brain Connections in Alzheimer's Rebuilt with New Peptide". GEN News Highlights. 11 October 2015. Retrieved 11 October 2015.
8. "Brain-Enhancing 'Smart Drugs' Are Going Commercial". VICE. 17 July 2014. Retrieved 11 October 2015.
9. "Prospective Alzheimer's drug builds new brain cell connections, improves cognitive function of rats". ScienceDaily. 11 October 2012. Retrieved 11 October 2015.
10. US patent 0337024, Allison Coffin, Joseph Harding, Leen Kawas, Phillip Uribe, "Novel Lead Compound for Otoprotection: Targeting HGF Signaling with Dihexa", issued 2015-11-26 
11. "Dihexa" (PDF). Alzheimer's Drug Discovery Foundation. August 13, 2021.
12. "Fosgonimeton | ALZFORUM". www.alzforum.org. Retrieved 2023-04-20.
13. "Fosgonimeton - Athira Pharma". AdisInsight. Springer Nature Switzerland AG.

• Antidementia agents
• Designer drugs
• Nootropics
• Peptides