Repurposing raltegravir for reducing inflammation and treating cancer: a bioinformatics analysis.

Autor: Nikfarjam Z; Department of Physical & Computational Chemistry, Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran., Rakhshi R; Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran., Zargari F; Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.; Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan (USB), Zahedan, Iran., Aalikhani M; Department of Medical Biotechnology, School of Paramedicine, Bushehr University of Medical Sciences, Bushehr, Iran., Hasan-Abad AM; Autoimmune Diseases Research Center, Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran., Bazi Z; Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran. zahrabazi1986@gmail.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Dec 05; Vol. 14 (1), pp. 30349. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1038/s41598-024-82065-8
Abstrakt: Inflammation is a defensive mechanism that safeguards the human body against detrimental stimuli. Within this intricate process, ADAM17, a zinc-dependent metalloprotease, emerges as an indispensable element, fostering the activation of diverse inflammatory and growth factors within the organism. Nonetheless, ADAM17 malfunctions can augment the rate of growth, inflammatory factors, and subsequent damage. Thus, in this study, we examined and repurposed drugs to suppress the activity of ADAM17. To this end, we employed bioinformatics techniques such as molecular docking, molecular dynamics, and pharmacokinetic studies. Five FDA-approved drugs including Raltegravir, Conivaptan, Paclitaxel, Saquinavir, and Venetoclax with the ability to impede the activity of the ADAM17 metalloenzyme were identified. Moreover, these drugs did not include strong zinc-binding functional groups when verified by the ACE functional group finder. However, further in silico analysis has indicated that Raltegravir demonstrates a commendable interaction with the active site amino acids and exhibits the most favorable pharmacokinetic properties compared to others. Considering the results of bioinformatics tools, it can be concluded that Raltegravir as an antiviral drug could be repurposed to prevent severe inflammatory response and tumorigenesis resulting from ADAM17 malfunction.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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