The GSK-3 inhibitors are useful tool in treating pathologies. Our laboratory develop specific GSK-3 inhibitors that are substrate competitive inhibitors, in contrast to other protein kinase inhibitors available that are ATP competitive inhibitors. Our strategy is based on understanding of how the enzyme recognizes and interacts with its substrates, and combines biochemical and computational analyses. Accordingly, we developed a novel class of substrate-competitive peptide inhibitors, headed by the compound “L803-mts”. In vivo inhibition of GSK-3 by L803-mts demonstrated its therapeutic benefits in diabetic, depressive behavior, and Alzheimer’s models.
- Research of signaling pathways of GSK-3 in neurodegenerative models.
- Structure/function analyses of GSK-3 iszoymes- at bioinfomatic and evolutionary perspectives.
- Design and develop new selective GSK-3 inhibitors, followed by testing in novel biological systems.