Identification of 4‐methoxythieno[2,3‐d]pyrimidines as FGFR1 Inhibitors

Kotey, I. M.; Protopopov, M. V.; Starosyla, S. A.; Balanda, A. O.; Pletnova, L. V.; Prykhod'ko, A. O.; Bdzhola, V. G.; Yarmoluk, S. M.

doi:10.7124/bc.0009A0

Biopolym. Cell. 2019; 35(2):152-162.

http://dx.doi.org/10.7124/bc.0009A0

Bioorganic Chemistry

Identification of 4‐methoxythieno[2,3‐d]pyrimidines as FGFR1 Inhibitors

1Kotey I. M., 1Protopopov M. V., 1Starosyla S. A., 1Balanda A. O., 1Pletnova L. V., 1Prykhod'ko 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 virtual screening approach. Methods. We used methods of organic synthesis, molecular docking via the Autodock 4.2.6 program package and in vitro biochemical tests with γ-³²P. Results. In vitro experiments showed that 9 of 23 tested compounds possess inhibitory activity against FGFR1 with IC₅₀ values in the range from 0.9 to 5.6 μM. Conclusions. Nine FGFR1 inhibitors were developed. The mode of compounds binding with the ATP-acceptor site was determined using molecular docking methods and the dependence of the compounds’ activity on the substituents R1, R4 and R5 was evaluated

Keywords: Fibroblast growth factor receptor 1, molecular docking, organic synthesis, in vitro testing, 4‐methoxythieno[2,3‐d]pyrimidin

Full text: (PDF, in English)

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