Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer's Disease.
Gilbert M RishtonGary C LookZhi-Jie NiJason ZhangYingcai WangYaodong HuangXiaodong WuNicholas J IzzoKelsie M LaBarberaColleen S LimegroverCourtney RehakRaymond YurkoSusan M CatalanoPublished in: ACS medicinal chemistry letters (2021)
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.
Keyphrases
- phase ii
- small molecule
- clinical trial
- open label
- computed tomography
- high throughput
- cognitive decline
- image quality
- contrast enhanced
- dual energy
- spinal cord
- type diabetes
- emergency department
- positron emission tomography
- binding protein
- blood brain barrier
- protein protein
- double blind
- study protocol
- drug induced
- mild cognitive impairment
- adverse drug
- single cell
- cerebral ischemia