Proteome Sciences said this week that is has achieved a milestone in the development of inhibitors to casein kinase 1 delta, the company's primary target in its Alzheimer's disease therapeutic program.
The company said it has demonstrated that two compounds – PS110 and PS278 – selected via in silico modeling and screening could lower tau phosphorylation levels in a human neuronal cell line model. Proteome Sciences now plans to test the two compounds in animal models, with the ultimate goal of taking them through to in vivo proof of concept and then partnering with an established pharmaceutical company, chief operating officer Ian Pike told ProteoMonitor.
The drug program stems from work the company did in collaboration with researchers at Kings College, London, on using mass spec to map post-translational modifications on tau, Pike said. Through this work, the company identified a number of previously undetected tau phosphorylation sites, many of them regulated by CK1d – suggesting its potential suitability as a drug target.
Over the last two years, the company has been using in silico modeling along with its pTau 2.0 & 3.0 selected-reaction monitoring mass spec assays for tau phosphorylation to profile potential inhibitors of the protein.
Having identified the two lead compounds, the company plans now to continue profiling them in further in vitro and in vivo pharmacokinetic studies and test their affects on cognition in animal models, Pike said.