Bioinfo Chem
System biology and Infochemistry
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Volume 7 Number 1 2025
RESEARCH ARTICLE (Open Access)
Computational Repurposing of Flavokawain B as a Novel p38 MAPK Inhibitor for Triple-Negative Breast Cancer Therapy
Abdullah Bhuyan1*, Shahadat Hossain2, Moin Uddin Patwary1, Shamim Al Mamun1, Tanjila Hasan Tulon1
Bioinfo Chem 7 (1) 1-8 https://doi.org/10.25163/bioinformatics.7110456
Submitted: 10 November 2024 Revised: 20 January 2025 Accepted: 25 January 2025 Published: 27 January 2025
Abstract
Background: Triple-Negative Breast Cancer (TNBC) is an aggressive and therapeutically challenging subtype with poor clinical outcomes. Among various oncogenic targets, p38 MAPK α (MAPK14) regulates key pathways in cell survival, apoptosis, and inflammatory responses. Despite its therapeutic relevance, MAPK14 remains underexplored in the context of natural compound–based interventions for TNBC. This study aims to fill that gap by evaluating plant-derived ligands with multi-targeted potential and better safety profiles as novel MAPK14 inhibitors for targeted cancer therapy.
Methods: This study employed a comprehensive in silico strategy to evaluate two phytochemicals, Epigallocatechin-3-gallate (EGCG) and Flavokawain B (FKB), as potential MAPK14 inhibitors. Molecular docking was performed using AutoDock Vina against the MAPK14 protein (PDB ID: 1A9U), followed by interaction visualization. ADME-Tox profiling was conducted using SwissADME and ProTox-II, while pathway analysis was performed via Cytoscape to explore downstream network connectivity.
Results: EGCG demonstrated high binding affinity (-8.0 kcal/mol) and diverse hydrogen bonding and π-type interactions, but showed limitations in GI absorption and bioavailability. In contrast, FKB exhibited slightly lower binding energy (-7.7 kcal/mol) but greater structural stability across docking poses, with superior pharmacokinetic features, including high GI absorption, BBB permeability, and low predicted toxicity. Network analysis indicated both compounds may influence apoptotic signaling via MAP2K3, TP53, and STAT1 pathways.
Conclusion: The results suggest that while EGCG shows strong molecular interactions, FKB presents a more balanced therapeutic profile. These findings support FKB as a promising natural inhibitor of MAPK14, warranting further in vitro and in vivo validation for TNBC therapy.
Keywords: Triple-Negative Breast Cancer (TNBC), p38 MAPK α (MAPK14), Epigallocatechin-3-gallate (EGCG), Flavokawain B (FKB), Molecular docking
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