Tyrosine Kinase Inhibitor: Genistein

　Genistein (1) is a specific inhibitor of tyrosine-specific protein kinase and the inhibition manner to EGF receptor kinase by 1 is ATP-competitive but non-competitive with the substrate, histone H2B.¹⁾ As shown in Table Ⅰ, 1 inhibits autophosphorylation of EGF receptor more potently than other flavonoids and isoflavonoids.¹⁾
Interestingly, 1 inhibits DNA topoisomerase II on the DNA cleavage assay basis (Table II). ²⁾ 1 also inhibits yeast α-glucosidase with a Ki value of 5.7×10^-8 M. ³⁾ The inhibition manner is non-competitive. 1 inhibits several enzymes in the following order of IC₅₀: α-glucosidase (50 nM), α-mannosidase (840 nM), β-mannosidase (4.5 μM), β-glucosidase (18 μM).

Table Ⅰ. Inhibition of genistein and related compounds to FGF receptor kinase¹⁾

Table Ⅱ. Inhibition of genistein to DNA topoisomerase II-mediated DNA cleavage activity²⁾