Fernandez-Sainz, JesúsPacheco-Linan, Pedro J.Granadino Roldán, José M.Bravo, IvanGarzón, AndrésRubio Martínez, JaimeAlbaladejo, Jose2022-07-112022-07-112017-07-011011-1344https://hdl.handle.net/2445/187566BI-2536 is a potent Polo-like kinase inhibitor which induces apoptosis in diverse human cancer cell lines. The binding affinity of BI-2536 for human serum albumin (HSA) protein may define its pharmacokinetic and pharmacodynamic profile. We have studied the binding of BI-2536 to HSA by means of different spectroscopic techniques and docking calculations. We have experimentally observed that the affinity of BI-2536 for HSA is higher than that of other common HSA binding drugs. Therefore, it can be postulated that the drug dose should be increased to achieve a certain concentration of free drug in plasma, although BI-2536 could also reach tumour tissues by uptaking HSA/BI-2536 complex. Only a single binding site on HSA has been observed for BI-2536 which seems to correspond to the subdomain IIA pocket. The formation of the HSA/BI-2536 complex is a spontaneous and entropy-driven process that does not cause a significant change of the secondary structure of the protein. Its endothermic character could be related to proton release. Thermodynamic analysis showed that the main protein-drug interactions are of the van der Waals type although the presence of amide and ether groups in BI-2536 could also allow H-bonding with some residues in the subdomain IIA pocket.11 p.application/pdfengcc-by-nc-nd (c) Elsevier B.V., 2017https://creativecommons.org/licenses/by-nc-nd/4.0/Medicaments antineoplàsticsAlbúminesFixació de proteïnesAntineoplastic agentsAlbuminsProtein bindinginfo:eu-repo/semantics/article6780612022-07-11info:eu-repo/semantics/openAccess