Status : Verified
| Personal Name | Mutia, Micah T. |
|---|---|
| Resource Title | In Silico Discovery of Potential Inhibitors Against Janus Kinases as Therapeutic Targets of Autoimmune Diseases Sourced from Phytochemicals of Philippine Plants |
| Date Issued | 6 July 2025 |
| Abstract | Autoimmune diseases arise from immune-mediated attacks on healthy tissues, driven by autoantibodies that target self-antigens and amplify inflammation through sustained activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Pro-inflammatory cytokines, often elevated in autoimmunity, hyperactivate JAK/STAT signaling, which in turn promotes autoreactive B and T cell responses, further increasing autoantibody production. This self-reinforcing cycle disrupts immune tolerance, perpetuates tissue damage, and accelerates disease progression, highlighting JAK/STAT as a critical node linking autoantibody-driven inflammation to autoimmune pathogenesis. While JAK inhibitors have proven effective in controlling such diseases, their clinical use has been limited by adverse effects, including increased risks of infections, cardiovascular events, and certain cancers. This study aimed to identify potential inhibitors of Janus kinases (JAK1, JAK2, JAK3, and TYK2), key components of the JAK/STAT pathway, by screening 2,607 phytochemicals from the MMRL virtual library. ADMETLab 3.0 was used to filter compounds based on drug-likeness and safety properties, and 24 candidates met all criteria for further analysis. Molecular docking analyses using AutoDock 4.2 and AutoDock VINA revealed that five promising candidates—cycloeicosane, ambrettolide, (10Z)- oxacyclononadec-10-en-2-one, (Z)-oxacyclopentadec-6-en-2-one, and myricetin 3- rutinoside—have competitive docking scores across all JAK kinases, comparable to or exceeding those of reference drugs such as peficitinib, upadacitinib, and tofacitinib. Molecular dynamics simulations indicated that these five phytochemicals are stable when in complex with the four Janus kinases within the 100-ns simulation timeframe. Hydrogen bond heatmaps highlighted the unique ability of myricetin 3-rutinoside to form consistent hydrogen bonds, while other candidates primarily relied on hydrophobic interaction |
| Degree Course | Master of Science in Chemical Engineering |
| Language | English |
| Keyword | molecular modeling; molecular dynamics; molecular docking; autoimmune diseases; phytochemicals; Philippine plants |
| Material Type | Thesis/Dissertation |
Preliminary Pages
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Category : P - Author wishes to publish the work personally.
Access Permission : Limited Access