A sharp increase in the incident of Alzheimer’s disease (AD) especially in developed and developing countries is a matter of serious concern. Current treatments for AD provide only modest symptomatic relief. There is an urgent need for ‘disease modifying’ agents that slow the course of the disease and prevent or delay the disease in susceptible individuals. Protein phosphorylation, the most common post-translational mechanism used by cells to regulate enzymes and structural proteins, is controlled by ≈520 protein kinases and ≈80 protein phosphatases. With the abovementioned rationale, the objective of this research is to discover novel lead molecules that are inhibitors of DYRK1A and CLK1 kinase with therapeutical potential in Alzheimer’s Disease. The availability of multiple crystal structures of DYRK1A and CLK1 complexed with inhibitors provides an opportunity for utilizing the structure based high-throughput virtual screening strategy for identifying potent and pharmacologically favourable inhibitors of DYRK1A and CLK1. With this understanding, the present research will employ a docking-based virtual screening technique to screen a commercially available chemical database against DYRK1A and CLK1 for identification of potent and diverse lead molecules with DYRK1A and CLK1 inhibitory activity. The identified lead molecules will be further optimized through SAR approach to give optimal candidates for translation into the clinic.

Alzheimer disease, CDC Like Kinase 1, DYRK1A gene