Discovery Of Investigational Drug Ct1812, An Antagonist Of The Sigma-2 Receptor Complex For Alzheimer'S Disease

An unbiased phenotypic neuronal assay was developed to measure the synaptotoxic effects of soluble A beta oligomers. A collection of CNS druglike small molecules prepared by conditioned extraction was screened. Compounds that prevented and reversed synaptotoxic effects of A beta oligomers in neurons were discovered to bind to the sigma-2 receptor complex. Select development compounds displaced receptor-bound A beta oligomers, rescued synapses, and restored cognitive function in transgenic hAPP Swe/Ldn mice. Our first-in-class orally administered small molecule investigational drug 7 (CT1812) has been advanced to Phase II clinical studies for Alzheimer's disease.