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Identification of highly selective type II kinase inhibitors with chiral peptidomimetic tails. | LitMetric
Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor potently inhibited Lck kinase with great selectivity (IC of 23.0 nM). It was found that and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that inhibited Lck activation in Jurkat T cells. Moreover, was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region.
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