The Discovery on Lead Compounds of Src Family Tyrosine Kinases Inhibitors

The src family tyrosine kinases participate in many signaling pathways, including proliferation, differentiation, and migration. Src family tyrosine kinases expressed in platelets, namely Fyn, Lyn, Src, Yes, Hck, and Src. Furthermore, four members, Hck, Fgr, Lyn, and Syk, are expressed in neutrophils. In this study, we focus on four kinases, Hck, Lyn, Syk and Src, and try to develop novel lead compounds. In previous study, a src tyrosine kinase inhibitor, 4-O-benzoyl-3-methoxy-β-nitrostyrene (BMNS), was synthesized and showed inhibitory effect on src tyrosine kinase with an IC50 value of 2.7 μM. In addition, BMNS also exhibited inhibitory effect on superoxide anion generation and elastase release induced by FMLP in human neutrophils with IC50 value of 0.5 μM. Therefore, the BMNS derivatives and other new src tyrosine kinase inhibitors will be designed, synthesized, evaluated, and developed using phamarcophore-based and fragment-based design. Finally, the pharmacokinetic analysis of bioactive derivatives will also be determined herein.

Project ID:PC10107-0048
External Project ID:NSC101-2320-B182-008