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Probing the interaction of Selonsertib with human serum albumin: In silico and in vitro approaches

Authors
 Mohammad Hassan Baig  ;  Preeti Gupta  ;  Mohd Imran Khan  ;  Mohamed F Alajmi  ;  Afzal Hussain  ;  Md Imtaiyaz Hassan  ;  Jae-June Dong 
Citation
 CURRENT TOPICS IN MEDICINAL CHEMISTRY, Vol.22(10) : 879-890, 2022-05 
Journal Title
CURRENT TOPICS IN MEDICINAL CHEMISTRY
ISSN
 1568-0266 
Issue Date
2022-05
Keywords
Anticancer therapy ; Drug development ; Human serum albumin ; Protein-drug interaction ; Selonsertib ; dynamics trajectories ; molecular level
Abstract
Introduction - Selonsertib, the most recently developed selective inhibitor of apoptosis signal-regulating kinase 1, was found to be highly productive in patients with stage 2 or 3 non-alcoholic steatohepatitis. We elucidated the binding characteristics, mechanism of interaction, and dynamic behaviors of selonsertib with human serum albumin (HSA), a major circulatory transport protein. Method- Different biophysical approaches (fluorescence quenching and isothermal titration calorimetry (ITC) were combined with various in silico techniques to examine the binding of selonsertib to HSA. Molecular docking results, analysis of molecular dynamics trajectories, and essential dynamics investigations indicated the stable binding of selonsertib to HSA. Further in vitro studies were performed to validate the observed interaction. Result- ITC results confirmed the robust binding and high affinity of selonsertib and HSA. Likewise, the fluorescence quenching results highlighted the binding affinity of selonsertib and HSA. Collectively, our findings offer deeper insight into the binding mechanism of selonsertib and HSA, emphasizing the selonsertib-mediated structural changes within HSA, along with a comprehensive rationale for the biological transport and accumulation of selonsertib in the blood plasma. Conclusion- Therefore, considering the bioavailability and effectiveness of selonsertib, assessing the interactions of this inhibitor with carrier proteins is crucial to elucidate its biological processes at the molecular level. This evidence carries the considerable scientific potential for future drug design.
Full Text
https://www.eurekaselect.com/article/122030
DOI
10.2174/1568026622666220330012032
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Family Medicine (가정의학교실) > 1. Journal Papers
Yonsei Authors
Dong, Jae June(동재준) ORCID logo https://orcid.org/0000-0002-2420-2155
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188670
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