Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer's Disease.
Basic Information
ID: ALA4837254
Journal: ACS Med Chem Lett
Title: Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer's Disease.
Authors: Rishton GM, Look GC, Ni ZJ, Zhang J, Wang Y, Huang Y, Wu X, Izzo NJ, LaBarbera KM, Limegrover CS, Rehak C, Yurko R, Catalano SM.
Abstract: An unbiased phenotypic neuronal assay was developed to measure the synaptotoxic effects of soluble Aβ oligomers. A collection of CNS druglike small molecules prepared by conditioned extraction was screened. Compounds that prevented and reversed synaptotoxic effects of Aβ oligomers in neurons were discovered to bind to the sigma-2 receptor complex. Select development compounds displaced receptor-bound Aβ 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.
CiteXplore: 34531947
DOI: 10.1021/acsmedchemlett.1c00048
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