<![CDATA[Colorectal cancer (CRC) is one of the diseases with the highest incidence rate in Indonesia and the world. Cancer treatment often uses natural compounds as an alternative treatment such as zerumbone in lempuyang rhizome. P38-Mitogen-activated protein kinase (MAPK) becomes the main target because it can regulate various cellular programs. Research was conducted to analyze the interaction of zerumbone and its derivatives against P38-MAPK proteins as potential anti-colorectal cancer. The method used was in silico using the pkCSM web, ProTox-II, Pubchem, SwissADME, and software such as Avogadro, AutoDockTools, BIOVIA Discovery Studio Visualizer. In Silico results of Dibenzosuberone compound as a natural ligand with a binding energy value of -13.05 kcal/mol, while the best test ligand is Derivat 21 with a binding energy value of -10.94 kcal/mol. Derivat 21 binds to the same active side as the natural ligand, namely: LEU104, LYS53, ALA51, ILE 84. ASP168, MET109, and ASP112. So that Derivat 21 has the potential as an anti-colorectal cancer drug that is more effective and safe compared to other compounds. Keywords: Zerumbone, Colorectal Cancer, P38-MAPK, In silico Abstrak Kanker kolorektal (colorectal cancer, CRC), salah satu jenis penyakit dengan tingkat kejadian tertinggi di Indonesia juga di dunia. Pengobatan kanker sering menggunakan senyawa alami sebagai pengobatan alternatif seperti zerumbone pada rimpang lempuyang. P38-Protein kinase teraktivasi mitogen (MAPK) menjadi target utama karena dapat mengatur berbagai program seluler. Penelitian dilakukan untuk menganalisis interaksi zerumbone dan derivatnya terhadap protein P38-MAPK sebagai potensi anti kanker kolorektal. Metode yang digunakan secara in silico menggunakan web pkCSM, ProTox-II, Pubchem, SwissADME, dan software seperti Avogadro, AutoDockTools, BIOVIA Discovery Studio Visualizer. Hasil In Silico senyawa Dibenzosuberone sebagai ligan alami dengan nilai binding energy -13,05 kkal/mol, Sedangkan ligan uji terbaik yaitu Derivat 21 dengan nilai binding energy -10,94 kkal/mol. Derivat 21 berikatan pada sisi aktif yang sama dengan ligan alami yaitu: LEU104, LYS53, ALA51, ILE 84. ASP168, MET109, dan ASP112. Sehingga Derivat 21 memiliki potensi sebagai obat anti kanker kolorektal yang lebih efektif dan aman dibandingkan dengan senyawa lainnya. Kata Kunci: Zerumbone, Kanker Kolorektal, P38-MAPK, In Silico]]>
