Evaluation of the binding behavior of olmutinib (HM61713) with model transport protein: Insights from spectroscopic and molecular docking studies

S C Olmutinib (HM61713, OMT), a novel third-generation tyrosine kinase inhibitor with good orally absorption, is able to inhibit selectively epidermal growth factor receptor mutations. In this work, the binding behavior of OMT with model transport protein bovine serum albumin (BSA) was assessed with the help of spectroscopic and molecular docking approaches. A fluorescence quenching of BSA was observed during the binding interaction of OMT with BSA, followed by a static mechanism was demonstrated. The affinity of OMT with BSA was moderate due to the binding constant of 2.75 x 10(5) M-1 at 293 K. The hydrophobic interactions, hydrogen bonds as well as van der Waals forces were acting as the predominant contributions in the OMT-BSA complexation process. The findings from site competitive experiments revealed that OMT tended to bind to subdomain IB (site III) of BSA, which was in keep with the outcomes of molecular docking studies. Based on synchronous and 3D fluorescence studies, we found that the conformation of BSA was changed owing to the binding with OMT. The FT-IR and UV-Vis studies further corroborated that the binding of OMT to BSA changed the secondary structure of BSA. Additionally, the experimental data showed that some metal ions (e.g. Ni2+, Fe3+, Mg2+, Cu2+) could promote the binding interaction of OMT with BSA. This study is beneficial to further assess the pharmacological properties of OMT and can provide valuable reference for designing new anti-tumor drugs. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

S C Olmutinib is a novel third-generation tyrosine kinase inhibitor that selectively targets epidermal growth factor receptor mutations. The binding behavior of OMT with bovine serum albumin was studied, revealing hydrophobic interactions, hydrogen bonds, and van der Waals forces as key factors in the complexation process. OMT tended to bind to subdomain IB of BSA, causing changes in BSA's conformation and secondary structure as observed through fluorescence, FT-IR, and UV-Vis studies.