Hit identification of FGFR1 inhibitors using receptor-based virtual screening

Tarnavskiy, S. S.; Protopopov, M. V.; Borovykov, O. V.; Pryhodko, A. O.; Bdzhola, V. G.; Yarmoluk, S. M.

doi:10.7124/bc.00099F

Biopolym. Cell. 2019; 35(2):143-151.

http://dx.doi.org/10.7124/bc.00099F

Bioorganic Chemistry

Hit identification of FGFR1 inhibitors using receptor-based virtual screening

1Tarnavskiy S. S., 1Protopopov M. V., 1Borovykov O. V., 1Pryhodko A. O., 1Bdzhola V. G., 1Yarmoluk S. M.

Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Aim. To identify novel FGFR1 inhibitors using the virtual screening approach. Methods. Virtual screening of a small organic compounds library was performed by molecular docking using the Autodock 4.2.6 program package. The compounds activity was determined by in vitro biochemical tests using γ-32P ATP. Results. In vitro experiments demonstrated that 18 compounds belonging to three chemical classes had an inhibitory activity against FGFR1 with IC₅₀ values in the range from 1.8 to 71 μM. Conclusions. Several FGFR1 inhibitors were found using molecular modeling and biochemical testing. These compounds are excellent candidates for further chemical optimization.

Keywords: Fibroblast growth factor receptor 1, molecular docking, virtual screening, in vitro testing

Full text: (PDF, in English)

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