University of Oulu

Cetinkaya A, Caglayan MG, Unal MA, Beyazkilic P, Elbuken C, Atici EB, Ozkan SA. Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches. Analytica. 2022; 3(1):144-160.

Investigation of pazopanib and human serum albumin interaction using spectroscopic and molecular docking approaches

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Author: Cetinkaya, Ahmet1; Caglayan, Mehmet Gokhan1; Unal, Mehmet Altay2;
Organizations: 1Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara 06560, Turkey
2Stem Cell Institute, Ankara University, Balgat, Ankara 06520, Turkey
3UNAM-National Nanotechnology Research Center, Institute of Materials Science and Nanotechnology, Bilkent University, Ankara 06800, Turkey
4Department of Chemical Engineering, Middle East Technical University, Ankara 06800, Turkey
5Faculty of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
6DEVA Holding A.S., R&D Center, Tekirdag 59510, Turkey
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 9.2 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2022
Publish Date: 2023-01-19


Pazopanib (PAZ), a tyrosine kinase inhibitor, is used to treat advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS). The FDA approved PAZ for RCC in 2009 and for STS in 2012. The antitumor activity of pazopanib, according to the degree of inhibition, shows different results depending on the dose. Renal cell carcinoma is the most sensitive carcinoma to pazopanib, with 77% inhibition at the 10 mg/kg dose. Clinical studies have shown 53% to 65% inhibition in carcinomas such as breast carcinoma, prostate carcinoma, and melanoma. Plasma proteins such as human serum albumin (HSA) have a critical role in transporting and storing bioactive components. This feature of HSA is very important for the development of cancer therapy. Here, we investigated the interaction between PAZ and HSA to evaluate their binding strength, binding types, and conformational change in HSA. We used spectroscopic methods to assess the drug–protein interaction. Fluorescence measurements revealed that the interaction of PAZ with HSA occurred via the static quenching mechanism. The calculated binding number and binding constants were 1.041 and 1.436 × 10⁶ M⁻¹, respectively, at 298.15 K based on fluorescence screening. The high binding constant and calculated Gibbs free energy at different temperatures showed spontaneous and strong binding. Circular dichroism measurements showed that the α-helix structure of HSA was retained as the secondary structure, with a slight reduction in its percentage after adding PAZ. Furthermore, molecular modeling studies suggested that the docking score of PAZ is higher than those of bicalutamide and ibuprofen, the drugs that were chosen as model competitors against PAZ. Accordingly, PAZ was found to replace bicalutamide and ibuprofen on the HSA binding site, which was also confirmed by UV absorption spectroscopy.

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Series: Analytica
ISSN: 2673-4532
ISSN-E: 2673-4532
ISSN-L: 2673-4532
Volume: 3
Issue: 1
Pages: 144 - 160
DOI: 10.3390/analytica3010011
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Copyright information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (