CAD-031 powder (CAD031) is a novel brain penetrant, J147-derivative that has enhanced neurogenic activity over J147 in human neural precursor cells (NPCs); also stimulates the division of NPCs in the subventricular zone of old APPswe/PS1E9 mice; rescues primary cortical neurons from oxytosis, and effectively reduce oxidative stress with EC50 of 20 nM; also prevents loss of energy metabolism that leads to neuron cell death in an in vitro ischemia model with EC50 of 47 nM; target fatty acid metabolism and inflammation, exhibits therapeutic efficacy on cognitive and physiological parameters in mouse model of AD.
CAD-031 powder were favorable in the context of preventing some of the toxic events in old age-associated neurodegenerative diseases. CAD-031 powder has potent neuroprotective properties in six distinct nerve cell assays that mimic toxicities observed in the old brain. Pharmacological and preliminary toxicological studies show that CAD-031 is brain-penetrant and likely safe. When fed to old, symptomatic APPswe/PS1ΔE9 AD mice starting at 10 months of age for 3 additional months in a therapeutic model of the disease, there was a reduction in the memory deficit and brain inflammation, as well as an increase in the expression of synaptic proteins. Small-molecule metabolic data from the brain and plasma showed that the major effect of CAD-031 is centered on fatty acid metabolism and inflammation. Pathway analysis of gene expression data showed that CAD-031 had major effects on synapse formation and AD energy metabolic pathways.
CAD-031 (2071209-49-7) Application
CAD-031 is broadly neuroprotective
CAD-031 has an excellent pharmacological and safety profile
CAD-031 reverses some aspects of cognitive dysfunction in old transgenic AD mice
RNA-seq analysis suggests that CAD-031 modulates inflammation, synaptic health, and metabolism
CAD-031 reduces inflammation and increases markers for neurogenesis and synapses
AD-31 targets lipid metabolism
CAD-031 (2071209-49-7) Reference
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