Chemistry:Dihexa
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.[1][2] The compound has been found to potently improve cognitive function in animal models of Alzheimer's disease-like mental impairment.[3][4][5][6][7][8][9][10][11] In an assay of neurotrophic activity, dihexa was found to be seven orders of magnitude more potent than brain-derived neurotrophic factor.[12]
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."[13]{{Citation needed|date=December 2021|
History
Dihexa was developed by Joseph Harding and his team at Washington State University.[14] Later developments were done by M3 Biotechnology, a company founded to commercialize dihexa.[15]
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[16]
References
- ↑ 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 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 PMID 25455861
- ↑ Harding JW, Wright JW, Benoist CC, Kawas LH, Wayman GA, "Hepatocyte growth factor mimics as therapeutic agents", US patent 8598118, issued 3 December 2013
- ↑ "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. October 2011. doi:10.1124/jpet.111.182220. PMID 21719467.
- ↑ "Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure". Frontiers in Cellular Neuroscience 9 (3): 3. January 2015. doi:10.3389/fncel.2015.00003. PMID 25674052.
- ↑ "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. January 2015. doi:10.3233/JAD-142814. PMID 25649658.
- ↑ "Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells". Stem Cell Reports 4 (5): 939–952. May 2015. doi:10.1016/j.stemcr.2015.04.001. PMID 25937370.
- ↑ "32. The Innovators: Designing Medicine's Holy Grail". KOMO News. 27 August 2015. http://komonews.com/sponsored/wsu125/32-the-innovators-designing-medicines-holy-grail.
- ↑ "Brain Connections in Alzheimer's Rebuilt with New Peptide". GEN News Highlights. 11 October 2015. http://www.genengnews.com/gen-news-highlights/brain-connections-in-alzheimer-s-rebuilt-with-new-peptide/81247461/.
- ↑ "Brain-Enhancing 'Smart Drugs' Are Going Commercial". VICE. 17 July 2014. https://www.vice.com/en/article/brain-enhancing-smart-drugs-are-going-commercial/.
- ↑ Ho JK, Nation DA. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies. Neurosci Biobehav Rev. 2018 Sep;92:209-225. doi:10.1016/j.neubiorev.2018.05.005 PMID 29733881
- ↑ "Prospective Alzheimer's drug builds new brain cell connections, improves cognitive function of rats". ScienceDaily. 11 October 2012. https://www.sciencedaily.com/releases/2012/10/121011090653.htm.
- ↑ 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
- ↑ "Dihexa". August 13, 2021. https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf.
- ↑ "Fosgonimeton | ALZFORUM". https://www.alzforum.org/therapeutics/fosgonimeton.
- ↑ "Fosgonimeton - Athira Pharma". AdisInsight. Springer Nature Switzerland AG. https://adisinsight.springer.com/drugs/800050463.
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