The Eph receptors have been implicated in variety of human cancers. Most of the current researches on the small molecule inhibitors of Eph receptors are focusing on the inhibition of EphA2, A4, B2 and B4 receptors. EphB3 receptor has been found overexpressed in several cancer cells and tumor tissues, such as pancreatic cancer, non-small-cell lung cancer and rhabdomyosarcoma; but few inhibitors were designed to target it. Here we have developed the first irreversible inhibitor of EphB3 kinase by modification of Dasatinib with a Michael acceptor to generate covalent bonding with the kinase. It has been demonstrated that the irreversible inhibitors are significantly more potent than their reversible counterparts after four-hour incubation and they have shown a time-dependent inhibition with EphB3 kinase. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/241nm/uploads/59619_figure1.jpg' alt='' />

Development of an irreversible inhibitor of EphB3 kinase

248th National Meeting (2014)

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