Flavones

One of the first discovered in the screening of inhibitors of FGFR1 classes are flavones. These compounds belong to a class of chromones which are widely represented in nature. They and their derivatives have long been known as inhibitors of protein kinases, including CDK. After primary search inhibitors of this class we find several compounds that inhibit FGFR1 with IC₅₀ in the range 3-5 µM. Molecular modeling confirmed their position in the binding site, similar to those obtained for structurally analogous inhibitors of CDK.

Figure 1. The binding mode of flavone inhibitor of FGFR1 in the ATP-binding site. Hydrogen bonds are shown by the dashed lines.

Flavone inhibitors FGFR1 with IC₅₀ less than 100 nM were found in further, but they had low selectivity of action. Non-specific inhibition is a known flavones problem, so optimization of this class as inhibitors of FGFR1 is not performed.

• А.А. Grischenko, V.G. Bdzhola, O.P. Kukharenko, S.M. Yarmoluk. Search for FGFR1 inhibitors among chromone derivatives. Ukrainica Bioorganica Acta 1 (2009) 50—56