Neuroscience Research Compound · For laboratory research use only
Also known as CAD-31
J147 ((E)-N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N'-(3-methoxybenzylidene)acetohydrazide) is a synthetic phenyl hydrazide described as a derivative of curcumin5,6. It was identified through a drug discovery scheme based on efficacy in multiple cell culture models of age-associated toxicities, rather than on a single disease-specific target1.
Published research is preclinical. Studies have examined it in transgenic and rapidly ageing mouse models, a scopolamine memory model, a mouse model of type 1 diabetes and rodent behavioural tests, along with its metabolism in liver microsomes1,2,3,4,5,6,7.
As described in the research literature
As described in the research literature, the originating group identified the mitochondrial alpha-F1 subunit of ATP synthase (ATP5A) as a molecular target of J147 in 2018. Targeting ATP synthase was reported to raise intracellular calcium and to produce sustained CAMKK2-dependent activation of the AMPK/mTOR pathway4.
Earlier work linked memory measures in aged transgenic Alzheimer's disease mice to induction of the neurotrophic factors NGF and BDNF and of several BDNF-responsive proteins2. A separate group reported that behavioural changes in mouse forced swim and tail suspension tests were accompanied by increased 5-HT1A receptor expression and by raised cAMP, PKA, phosphorylated CREB and BDNF, and were blocked by the 5-HT1A antagonist WAY-1006356.
What published studies have examined
The 2011 study describing J147 examined synaptic protein loss and cognitive measures in a transgenic Alzheimer's disease mouse model and memory in normal rodents1. A 2013 study treated aged APP/swePS1deltaE9 mice at an advanced stage of pathology, measuring memory, amyloid metabolism and neurotrophic pathways, and compared J147 with donepezil in a scopolamine model2.
A multiomics study in old and young SAMP8 mice examined protein and gene expression, metabolite levels and cognition3. The ATP synthase target study examined age-associated drift of the hippocampal transcriptome and plasma metabolome in mice and lifespan in Drosophila4.
In streptozotocin-induced diabetic mice, sciatic nerve conduction velocity, touch-evoked allodynia, TNF-alpha pathway markers of neuroinflammation and RNA expression profiles pointing to AMP kinase pathway activation were examined5.
Sources [5]
Forced swim and tail suspension tests in mice were used with receptor antagonists to examine serotonin receptor involvement6. Metabolites of J147 were characterised in human and mouse liver microsomes and mouse plasma; the study reported that it is not metabolised to aromatic amines or hydrazines and that its oxidative metabolites were also active in neuroprotection assays7.
A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.
Chen Q, Prior M, Dargusch R, et al. PLoS One, 2011.
The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice.
Prior M, Dargusch R, Ehren JL, et al. Alzheimer's Research & Therapy, 2013.
A comprehensive multiomics approach toward understanding the relationship between aging and dementia.
Currais A, Goldberg J, Farrokhi C, et al. Aging, 2015.
The mitochondrial ATP synthase is a shared drug target for aging and dementia.
Goldberg J, Currais A, Prior M, et al. Aging Cell, 2018.
A novel curcumin derivative for the treatment of diabetic neuropathy.
Daugherty DJ, Marquez A, Calcutt NA, et al. Neuropharmacology, 2018.
Antidepressant-like effects of a novel curcumin derivative J147: Involvement of 5-HT(1A) receptor.
Lian L, Xu Y, Zhang J, et al. Neuropharmacology, 2018.
Metabolism of a potent neuroprotective hydrazide.
Chiruta C, Zhao Y, Tang F, et al. Bioorganic & Medicinal Chemistry, 2013.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.