Development of Irreversible Inhibitors of MELK Kinase

摘要

We have performed 3 rounds of in silico docking combined with in vitro MELK kinase activity assays. We have identified 5 independent scaffolds capable of MELK inhibition in the range of 100nm-1um. These compounds are capable to tightly bind MELK catalytic domain as measured by DCS, ruling out the protein aggregation and other non-specific inhibiotry modalities. These leads are now being developed into potent anti-MELK drugs.