CAD031

CAD031 is an orally active AMPK/ACC1 signaling pathway activator and a derivative of the Alzheimer's disease (AD) targeted agent J147 (HY-13779) (more active than J147 in human neural stem cell assays). CAD031 can cross the blood-brain barrier, activate AMPK and inhibit ACC1, thereby increasing ac-CoA levels, improving mitochondrial function and reducing free fatty acid synthesis. CAD031 has neuroprotective, neurogenesis-promoting and memory-improving activities and can be used in the study of Alzheimer's disease and aging-related neurodegenerative diseases. CAD031 effectively enhances the memory of mice, improves dendritic structure, and stimulates cell division in the germinal zone of the brain of elderly mice^[1][2][3]. In Vitro:CAD031 (100 nM; 7 d) significantly induces the mRNA expression of neurogenesis markers Nestin, Pax6, DCX, and Ki67 in human neural precursor cells (hNPCs) experiments; and 1 μM CAD031 inhibits Aβ-induced cell death in MC65 cells and glutamate-induced cytotoxicity in HT22 cells, exerting neuroprotective activity^[1]. In Vivo:CAD031 (200 ppm; dietary administration; daily; 6 months) improves fear conditioning and spatial pattern separation memory, increases neural precursor cell proliferation in the dentate gyrus and subventricular zone, without affecting Aβ plaque burden in the APP^swe/PS1^ΔE9 transgenic AD mouse model^[1].
CAD031 (200 ppm; dietary administration; daily; 4 months) extends median lifespan, maintained mitochondrial gene expression and protein levels, reduces plasma free fatty acids, and activates the hepatic AMPK/ACC1 pathway in rapidly aging SAMP8 mice^[2].