Discovery of dual ZAP70 and Syk kinases inhibitors by docking into a rare C-helix-out conformation of Syk

Zhao, Hongtao; Caflisch, Amedeo

doi:10.1016/j.bmcl.2014.01.083

Citations

Citation copied

Zhao, H., & Caflisch, A. (2014). Discovery of dual ZAP70 and Syk kinases inhibitors by docking into a rare C-helix-out conformation of Syk. Bioorganic & Medicinal Chemistry Letters, 24(6), 1523–1527. https://doi.org/10.1016/j.bmcl.2014.01.083

Abstract

The non-receptor tyrosine kinase Syk (spleen tyrosine kinase) is a pharmaceutical relevant target because its over-activation is observed in several autoimmune diseases, allergy, and asthma. Here we report the identification of two novel inhibitors of Syk by high-throughput docking into a rare C-helix-out conformation published recently. Interestingly, both compounds are slightly more active on ZAP70 (Zeta-chain-associated protein kinase 70), which is the kinase closest to Syk in the phylogenetic tree of human kinases. Taken together,