Biomolecular interactions and binding dynamics of tyrosine kinase inhibitor erdafitinib, with human serum albumin.

Erdafitinib is an approved tyrosine kinase inhibitor that inhibits fibroblast growth factor receptor. It has been described as one of the potent anti-tumor drugs especially for the treatment of urothelial carcinoma. In this study, we have investigated the binding dynamics of erdafitinib with human serum albumin (HSA) using multiple spectroscopic techniques. The outcome of the results suggests the occurrence of static quenching during the interaction of HSA with erdafitinib which leads to the formation of non-fluorescent HSA-erdafitinib ground state complex. Formation of HSA-erdafitinib complex was also confirmed from the findings of absorption spectral analysis. The changes in microenvironment around hydrophobic domains (especially tryptophan and tyrosine) were deciphered from fluorescence spectroscopy which was further confirmed by synchronous spectral analysis. In order to gain insight into the binding site of erdafitinib in HSA, molecular docking combined with competitive displacement assay was performed. The modified form of Stern Volmer equation was used to estimate various binding parameters including number of binding sites. The findings are indicative of a single binding site (n = 1) with binding constant in the order of 104. The negative values of thermodynamic parameters like ΔG, ΔH and ΔS were suggestive of the binding reaction being spontaneous and exothermic, while the hydrogen bonds and Van der Waals interactions being the major forces present between HSA and erdafitinib. Circular dichroism spectral analysis revealed the alterations in the conformation of HSA structure and reduction in its α-helical content.Communicated by Ramaswamy H. Sarma[Formula: see text].