Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with the accumulation of the neurotoxic peptide Amyloid β (Αβ). Casein kinase 1 family comprises of eight isozymes, two of which CK1δ and CK1ε are predominantly expressed in the brain. CK1δ plays a critical role in AD through phosphorylation of tau, a protein associated with microtubules, which precedes neuritic lesion formation, implicating CK1δ in the tau fibrillization reaction pathway. CK1δ has been reported to be associated with pathological accumulation of tau in several neurodegenerative diseases including AD, Down syndrome, progressive supranuclear palsy, and parkinsonism dementia complex of Guam. Inhibition of CK1δ has been shown to reduce fibrillar lesions and to inhibit Aβ production. Our recent work investigating quinones as kinase inhibitors revealed a quinone compound that inhibited CK1δ and Pim1 kinase preferentially over CK1γ2 and 98 other human protein kinases. Similarity search and preliminary in-vitro CK1δ kinase inhibition assay have yielded a few compounds with good potency.

Development of novel casein kinase 1 nhibitors

249th National Meeting (2015)

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