Selectivity-determining residues in Plk1.

摘要: Polo-like kinase 1 is an important regulator of cell cycle progression whose over-expression often associated with oncogenesis. hence represents attractive target for cancer intervention. BI 2536 (Boehringer Ingelheim, Germany), a inhibitor currently in clinical trials, exhibits nanomolar potency against isoforms and high selectivity other kinases. We have previously published the crystal structures domain complex AMPPNP Aurora A inhibitor. In this work, we present co-crystal structure 2536. The structure, combination data related compounds, illustrates features selectivity. particular, show that methoxy group specificity determinant non-Polo-like kinases by taking advantage small pocket generated Leu 132 hinge region 1. work presented here provides framework structure-based drug design 1-specific inhibitors.