Hit identification of FGFR1 inhibitors using receptor-based virtual screening

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. K e y w o r d s: Fibroblast growth factor receptor 1, molecular docking, virtual screening, in vitro testing.

In Silico Screening and Anticancer-Apoptotic Evaluation of Newly Synthesized Thienopyrimidine/Sulfonamide Hybrids

“…Replacing the cyclohexyl side chain with an open ester one (R1) and a methyl group (R2) was carried out to further explore the effect of this replacement on biological activity and compare results between a cyclic side chain and the open one. Furthermore, sulfonamides had been previously incorporated in compounds resulting in promising anticancer activity, especially kinase inhibition profiles [ 18 , 19 , 20 ]. Accordingly, it prompted our interest to link the coplanar cyclic structure of thienopyrimidine with different substituted sulfonamide groups which were incorporated in the thienopyrimidine core at position 4 to afford two novel series of thienopyrimidine–sulfonamide hybrids “series a from 1a – 4a ( i – iii )” and “series b from 1b – 4b ( i – iii )”, aiming to explore their biological anticancer and apoptotic activities ( Figure 1 ).…”