Abstract
Enasidenib (EDB) is a new therapeutic agent for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. This research aimed at utilizing experimental and theoretical approaches to characterize the binding mechanism between EDB and human serum albumin (HSA). Formation of an EDB-HSA static complex was demonstrated by quenching of the HSA intrinsic fluorescence by EDB. Using well known mathematical relations (e.g. Stern-Volmer and Lineweaver-Burk equations), the recorded EDB-HSA fluorescence data were interpreted and revealed binding constants in the magnitude order of 10
M
for the different investigated temperatures. These determined results were taken into further mathematical calculations to reveal the thermodynamic properties of EDB-HSA binding. Results demonstrated that spontaneous EDB and HSA binding takes place led by electrostatic forces. Computational docking studies have further confirmed the latter finding showing that EDB fits into the HSA Sudlow site I. Molecular dynamic simulation was performed to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R
) and hydrogen bond parameters for the EDB-HSA complex.