J147

J147
Legal status
Legal status
Identifiers
  • N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N-[(E)-(3-methoxyphenyl)methylideneamino]acetamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H17F3N2O2
Molar mass350.341 g·mol−1
3D model (JSmol)
  • CC1=C(C=CC(=C1)C)N(C(C(F)(F)F)=O)\N=C\C2=CC(=CC=C2)OC
  • InChI=1S/C18H17F3N2O2/c1-12-7-8-16(13(2)9-12)23(17(24)18(19,20)21)22-11-14-5-4-6-15(10-14)25-3/h4-11H,1-3H3/b22-11+
  • Key:HYMZAYGFKNNHDN-SSDVNMTOSA-N

J147 is an experimental drug with reported effects against both Alzheimer's disease and ageing in mouse models of accelerated aging.

The approach that lead to development of the J147 drug was to screen candidate molecules for anti-aging effects, instead of targeting the amyloid plaques. It is contrary to most other approaches to developing drugs against Alzheimer's disease that target the plaque deposits in the brain.

The J147 drug is also reported to address other biological aging factors, such as preventing the leakage of blood from microvessels in mice brains. The development of J147 follows the chemical pharmacological way, contrary to biological ways that exploit e.g. use of bacteriophages.

Its derivative CAD-31 has enhanced neurogenic activity over J147 in human neural precursor cells. CAD-31 enhances the use of free fatty acids for energy production by shifting of the metabolic profile of fatty acids toward the production of ketone bodies, the only alternative source of energy in the brain when glucose levels are low.

The target molecule is a protein called ATP synthase, which is found in the mitochondria.

References

  1. ↑ "Experimental drug targeting Alzheimer's disease shows anti-aging effects" (Press release). Salk Institute. 12 November 2015. Retrieved November 13, 2015.
  2. ↑ Chen Q, Prior M, Dargusch R, Roberts A, Riek R, Eichmann C, Chiruta C, Akaishi T, Abe K, Maher P, Schubert D (14 December 2011). "A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease". PLoS One. 6 (12) e27865. Bibcode:2011PLoSO...627865C. doi:10.1371/journal.pone.0027865. PMC 3237323. PMID 22194796.
  3. ↑ Currais A, Goldberg J, Farrokhi C, Chang M, Prior M, Dargusch R, Daugherty D, Armando A, Quehenberger O, Maher P, Schubert D (11 November 2015). "A comprehensive multiomics approach toward understanding the relationship between aging and dementia". Aging. 7 (11): 937–55. doi:10.18632/aging.100838. PMC 4694064. PMID 26564964.
  4. ↑ Prior M, Dargusch R, Ehren JL, Chiruta C, Schubert D (May 2013). "The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice". Alzheimer's Research & Therapy. 5 (3) 25. doi:10.1186/alzrt179. PMC 3706879. PMID 23673233. Archived from the original on 2015-11-23. Retrieved 2015-11-22.
  5. 1 2 Brian L. Wang (13 November 2015). "Experimental drug targeting Alzheimer's disease shows anti-aging effects in animal tests". nextbigfuture.com. Retrieved November 16, 2015.
  6. ↑ Krishnan R, Tsubery H, Proschitsky MY, Asp E, Lulu M, Gilead S, Gartner M, Waltho JP, Davis PJ, Hounslow AM, Kirschner DA, Inouye H, Myszka DG, Wright J, Solomon B, Fisher RA (2014). "A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies". Journal of Molecular Biology. 426 (13): 2500–19. doi:10.1016/j.jmb.2014.04.015. PMID 24768993.
  7. ↑ Solomon B (October 2008). "Filamentous bacteriophage as a novel therapeutic tool for Alzheimer's disease treatment". Journal of Alzheimer's Disease. 15 (2): 193–8. doi:10.3233/jad-2008-15205. PMID 18953108.
  8. ↑ Daugherty, D., Goldberg, J., Fischer, W., Dargusch, R., Maher, P., & Schubert, D. (2017). A novel Alzheimer's disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimer's research & therapy, 9(1), 50. https://doi.org/10.1186/s13195-017-0277-3 This article incorporates text from this source, which is available under the CC BY 4.0 license.
  9. ↑ "Researchers identify the molecular target of J147, which is nearing clinical trials to treat Alzheimer's disease". Retrieved 2018-01-30.