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Kinome,which refers to the entire kinase groups in an organism,is composed of over 500 different kinases.Extracellular stimuli transmit signals into a cell by activating their target kinases.Several kinases are found to act as upstream mediators to regulate signaling molecules involved in chronic inflammatory diseases.Therefore,identification of new functional agents which can directly suppress the function of target kinases is now regarded as rational approach to prevent chronic inflammatory diseases including cancer.As an example,Src (Src,Fyn,Lyn),a family of proto-oncogenic tyrosine kinases activated by a variety ofproinflammatory agents,is known to regulate cell proliferation,differentiation,survival,and angiogenesis.Src family subsequently activates downstream signal cascade including RAF-MEK-ERK and PI3K-Akt,thereby inducing cell proliferation and causing chronic inflammatory diseases including cancer.Our study focused on finding naturally derived phytochemicals which exert cancer-preventive effects and investigating the molecular mechanism underlying their effect.We have reported that the chemopreventive action of quercetin,myricetin,procyanidin B2,and equol occurs by directly binding to their target kinase,Fyn,Src,Raf,and MEK,respectively,thereby inhibiting cell growth and inflammation.Caffeic acid,a metabolite of chlorogenic acid,binds to and inhibits Fyn,MEK,and TOPK,thereby suppressing inflammation,cell growth and cancer metastasis (Carcinogenesis,2009; Gastroentenology,submitted).Our current study primarily aims to find small molecules regulating target kinases such as Fyn,JNK2,vanilloid receptor,related to carcinogenesis,through molecular modeling with natural compound database,and to investigate their modes of action using X-ray crystallography.