The First Molecular-Scale View of Cabozantinib–Human Serum Albumin Binding: Quantitative Spectroscopic Insights

Authors : Cem Erkmen

Pages : 337-345

Doi:10.7240/jeps.1732487

View : 120 | Download : 172

Publication Date : 2025-12-23

Article Type : Research Paper

Abstract :This study aims to examine, for the first time, the interaction between the tyrosine kinase inhibitor cabozantinib (CAB) and human serum albumin (HSA), emphasizing the binding mechanism, affinity, and possible structural alterations by fluorescence spectroscopy. The association between CAB and HSA was predominantly explored through fluorescence spectroscopic analysis. To evaluate this interaction, a set of quenching measurements was systematically carried out by titrating increasing concentrations of CAB into a fixed concentration of HSA solution. Temperature-dependent measurements were also conducted to analyze the quenching mechanism and to calculate thermodynamic parameters. Stern-Volmer analysis, as well as double logarithmic fitting, were used to evaluate the quenching behavior and binding affinity. The progressive decrease of HSA’s native fluorescence upon incremental addition of CAB concentrations indicated the formation of the CAB-HSA complex. A noticeable reduction in Stern-Volmer quenching constants (KSV) was recorded as the temperature increased, suggesting a static quenching mechanism. Binding constants (Ka) were found to be in the order of 104 M-1, pointing to a relatively intermediate affinity between CAB and HSA, compatible with its transport in blood plasma. The spontaneity of the binding was supported by thermodynamic data, highlighting hydrophobic interactions as the principal contributor, in combination with hydrogen bonding and weak van der Waals attractions. In addition, no shifts in emission maxima and significant fluorescence quenching around tryptophan and tyrosine residues indicated microenvironmental perturbations, suggesting localized conformational changes in the protein structure upon CAB binding.
Keywords : Kabozantinib, Kanser, Floresans Spektroskopisi, İnsan Serum Albumini, UV-Görünür Spektroskopisi

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