Potensi Seskuiterpen Lakton dari Vernonia amygdalina sebagai Inhibitor JAK1 pada Kanker Payudara Overekspresi HER-2

Hanifah Sabrina, Denny Satria

Abstract


Jalur pensinyalan JAK/STAT memiliki peran penting dalam perkembangan kanker payudara yang menunjukkan overekspresi HER-2, yaitu tipe yang lebih agresif dan berkaitan dengan prognosis yang buruk serta ketahanan terhadap terapi. Penelitian ini menerapkan metode in silico untuk menyelidiki kapasitas senyawa seskuiterpen lakton dari Vernonia amygdalina sebagai penghambat JAK1. Sebanyak lima belas senyawa dianalisis dengan menggunakan Molecular docking dan simulasi Molecular Dynamics (MD) selama 100 ns. Validasi dari proses docking menunjukkan hasil yang memuaskan dengan nilai RMSD sebesar 0,616 Å. Vernolepin ditentukan sebagai senyawa utama karena memiliki afinitas pengikatan yang lebih baik dibandingkan dengan ruxolitinib (-8,2 kcal/mol) dan berinteraksi dengan residu-residu penting seperti Val889 dan Phe958. Hasil dari simulasi MD mengindikasikan bahwa kompleks JAK1-Vernolepin lebih stabil jika dibandingkan dengan ruxolitinib, terlihat dari nilai RMSD yang rendah (0,2-0,4 Å), RMSF yang konsisten, struktur yang kompak (Rg), nilai SASA yang stabil, serta rata-rata sekitar lima ikatan hidrogen. Analisis MM-PBSA juga menunjukkan bahwa energi pengikatan yang diperoleh lebih tinggi (105,82 kJ/mol). Temuan ini menegaskan bahwa vernolepin berpotensi menjadi kandidat sebagai inhibitor JAK1 untuk mengatasi ketahanan dalam kasus kanker payudara overekspresi HER-2.

Keywords


Kanker payudara; JAK1; Seskuiterpen Lakton; Vernonia amygdalina; In Silico

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References


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DOI: https://doi.org/10.31764/lf.v7i2.39217

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