Elucidation of binding dynamics of tyrosine kinase inhibitor tepotinib, to human serum albumin, using spectroscopic and computational approach

Tepotinib (TPT), an anticancer drug, is a fibroblast growth factor receptor inhibitor approved by the FDA for the chemotherapy of urothelial carcinoma. The binding of anticancer medicines to HSA can affect their pharmacokinetics and pharmacodynamics. The absorption, fluorescence emission, circular dichroism, molecular docking, and simulation studies were used to evaluate the binding relationship between TPT and HSA. The absorption spectra exhibited a hyperchromic effect upon the interaction of TPT with HSA. The Stern-Volmer and binding constant of the HSA-TPT complex demonstrates that fluorescence quenching is triggered by a static rather than a dynamic process. Further, the displacement assays and molecular docking results revealed that TPT preferred binding to site III of HSA. Circular dichroism spectroscopy confirmed that TPT binding to HSA induces conformational changes and reduces α-helical content. The thermal CD spectra reveal that tepotinib enhances protein's stability in the temperature range of 20 to 90 °C. The findings of MDS studies provide further evidence for the stability of the HSA-TPT complex. Consequently, the findings of the present investigation provide a clear picture of the impacts of TPT on HSA interaction. These interactions are thought to make the microenvironment around HSA more hydrophobic than in its native state. [Display omitted] •The ground state complex formation was confirmed between HSA and tepotinib (TPT).•Binding of TPT is spontaneous, exothermic and decreases α-helical content of HSA.•In the temperature range of 20–90 °C, the HSA-TPT complex was more stable than HSA alone.•TPT binds in drug binding site III and the stability of the complex was supported by MDS.