Molecular Docking, Molecular Dynamics Simulation, and Pharmacophore-Based Virtual Screening Unveil Natural Compounds with TIM-3 Inhibitory Activity

Introduction: The aberrant expression of T cell immunoglobulin mucin-3 (TIM-3) has been linked to adaptive immunotherapy resistance and poor prognosis. Targeting TIM-3 has gained popularity due to positive outcomes in preclinical settings. Materials and method: This research explored the Supernatura...

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Main Authors: Abdulrahim A. Alzain, Mohammed A. Almogaddam, Rayan Yousif, Mohammed Hamed Alqarni, Ahmed I. Foudah, Wadah Osman, Khaled M. Elamin, Hagar M. Mohamed, Ehssan Moglad, Ahmed Ashour, Reham M. Samra, Gamal A. Mohamed, Sabrin R.M. Ibrahim
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-06-01
Series:Journal of Pharmacy and Bioallied Sciences
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Online Access:https://journals.lww.com/10.4103/jpbs.jpbs_402_25
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Summary:Introduction: The aberrant expression of T cell immunoglobulin mucin-3 (TIM-3) has been linked to adaptive immunotherapy resistance and poor prognosis. Targeting TIM-3 has gained popularity due to positive outcomes in preclinical settings. Materials and method: This research explored the Supernatural 3.0 database for potential TIM-3 inhibitors. A pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations were conducted for 449,008 compounds. Compounds SN0085417 (-7.542 kcal/mol), SN0261906 (-7.036 kcal/mol), and SN0276180 (-6.871 kcal/mol) showed better docking scores. These compounds revealed remarkable hydrogen bonds and π–π stackings interactions with TIM-3 IgV domain. Results: The analysis of root-mean-square deviation (RMSD) and root-meansquare-fluctuation (RMSF) trajectories displayed stable interaction patterns with no substantial conformational changes in the TIM-3 backbone. Conclusion: These findings proposed SN0085417, SN0276180, and SN0261906 as TIM-3 inhibitors, which, with more extensive analysis, could undoubtably add to the realm of feasible TIM-3 based cancer immunotherapies.
ISSN:0976-4879
0975-7406