Studi In Silico Senyawa Aktif Gambir (Uncaria gambir) sebagai Inhibitor KRAS G12D pada Kanker Pankreas In Silico Study of Active Compounds of Gambir (Uncaria gambir) as KRAS G12D Inhibitors in Pancreatic Cancer

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Page Numbers: 1125-1142
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Published: Apr 27, 2026
Digital Object Identifier: 10.58578/masaliq.v6i3.9742
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Vioni Yulianti1, Okta Suryani2*
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Vioni Yulianti
Universitas Negeri Padang
Okta Suryani
Universitas Negeri Padang

Abstract

Although pancreatic cancer, particularly PDAC with the KRAS G12D mutation, has been the focus of various studies, research specifically evaluating the potential of active compounds from Uncaria gambir as KRAS G12D inhibitors through an in silico approach remains limited. This study aimed to analyze the binding affinity, drug-likeness profile, and ADMET parameters of active compounds from Uncaria gambir against the KRAS G12D protein. This study used a computational approach through molecular docking and virtual screening designs involving seven test compounds with the KRAS G12D protein structure (PDB ID: 7RPZ), using MRTX1133 as a positive control. The data were analyzed based on binding affinity, RMSD, Lipinski’s Rule of Five, Veber parameters, and ADMET evaluation. The results showed that roxburghine had the highest affinity (−6.7780 kcal/mol), but did not meet Lipinski’s criteria and was indicated to be hepatotoxic. Gambirine and isogambirine were detected as mutagenic and hepatotoxic, whereas quercetin was considered the most prospective because it had a binding affinity of −5.1256 kcal/mol, an RMSD of 1.0570 Å, and interactions with GLU63, HIS95, and GLN99 residues through H-acceptor bonds, accompanied by a superior pharmacokinetic and safety profile. The conclusion of this study confirms that active compounds from Uncaria gambir, particularly quercetin, have the potential to be further explored as candidate KRAS G12D inhibitors in pancreatic cancer, while also providing an initial contribution to the development of natural compounds based on computational approaches in anticancer research.

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How to Cite
Yulianti, V., & Suryani, O. (2026). Studi In Silico Senyawa Aktif Gambir (Uncaria gambir) sebagai Inhibitor KRAS G12D pada Kanker Pankreas. MASALIQ, 6(3), 1125-1142. https://doi.org/10.58578/masaliq.v6i3.9742

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References

Ajmal, A., Danial, M., Zulfat, M., Numan, M., Zakir, S., Hayat, C., Alabbosh, K. F., Zaki, M. E. A., Ali, A., & Wei, D. (2024). In silico prediction of new inhibitors for Kirsten rat sarcoma G12D cancer drug target using machine learning-based virtual screening, molecular docking, and molecular dynamic simulation approaches. Pharmaceuticals, 17(5), 551. https://doi.org/10.3390/ph17050551

Ayad, L. A. K., Pissis, S. P., & Polychronopoulos, D. (2018). CNEFinder: Finding conserved non-coding elements in genomes. Bioinformatics, 34(17), i743–i747. https://doi.org/10.1093/bioinformatics/bty601

Besson-Bard, A., & Wendehenne, D. (2009). NO contributes to cadmium toxicity in Arabidopsis thaliana by mediating an iron deprivation response. Plant Signaling & Behavior, 4(3), 252–254. https://doi.org/10.4161/psb.4.3.8032

Choucair, K., Imtiaz, H., Uddin, M. H., Nagasaka, M., Al-Hallak, M. N., Philip, P. A., El-Rayes, B., Pasche, B. C., & Azmi, A. S. (2025). Targeting KRAS mutations: Orchestrating cancer evolution and therapeutic challenges. Signal Transduction and Targeted Therapy, 10, 385. https://doi.org/10.1038/s41392-025-02473-8

Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717

Huang, L., Guo, Z., Wang, F., & Fu, L. (2021). KRAS mutation: From undruggable to druggable in cancer. Signal Transduction and Targeted Therapy, 6, 386. https://doi.org/10.1038/s41392-021-00780-4

Jančík, S., Drábek, J., Radzioch, D., & Hajdúch, M. (2010). Clinical relevance of KRAS in human cancers. Journal of Biomedicine and Biotechnology, 2010, 150960. https://doi.org/10.1155/2010/150960

Kappan, M. M., & George, J. (2023). In silico pharmacokinetic and molecular docking studies of natural plants against essential protein KRAS for treatment of pancreatic cancer. Journal of Natural Remedies, 23(3), 1108–1122. https://doi.org/10.18311/jnr/2023/31947

Kargbo, R. B. (2025). Targeting KRAS G12D and G10 mutations with novel small molecule inhibitors. ACS Medicinal Chemistry Letters, 16(6), 939–941. https://doi.org/10.1021/acsmedchemlett.5c00264

Kim, H., Shim, H., Ranganath, A., He, S., Stevenson, G., & Allen, J. E. (2025). Protein-ligand binding affinity prediction using multi-instance learning with docking structures. Frontiers in Pharmacology, 15, 1518875. https://doi.org/10.3389/fphar.2024.1518875

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46(1–3), 3–26. https://doi.org/10.1016/S0169-409X(00)00129-0

Ma, Z., Ajibade, A., & Zou, X. (2024). Docking strategies for predicting protein-ligand interactions and their application to structure-based drug design. Communications in Information and Systems, 24(3), 199–230. https://doi.org/10.4310/CIS.241021221101

Magfirah, N., & Hala, Y. (2025). CRISPR/Cas9 untuk Canonical Mutations pada Kanker Pankreas: Harapan Baru Terapi Presisi. Empiricism Journal, 6(4), 1855–1870. https://doi.org/10.36312/ej.v6i4.3594

Mat Saad, M. F., Goh, H.-H., Rajikan, R., Tuan Yusof, T. R., Baharum, S. N., & Bunawan, H. (2020). Uncaria gambir (W. Hunter) Roxb: From phytochemical composition to pharmacological importance. Tropical Journal of Pharmaceutical Research, 19(8), 1767–1773. https://doi.org/10.4314/tjpr.v19i8.28

McKerrow, J. H., & Lipinski, C. A. (2017). The rule of five should not impede anti-parasitic drug development. International Journal for Parasitology: Drugs and Drug Resistance, 7(2), 248–249. https://doi.org/10.1016/j.ijpddr.2017.05.003

Munggari, I. P., Kurnia, D., Deawati, Y., & Julaeha, E. (2022). Current research of phytochemical, medicinal and non-medicinal uses of Uncaria gambir Roxb.: A review. Molecules, 27(19), 6551. https://doi.org/10.3390/molecules27196551

Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104

Prinsa, Saha, S., Bulbul, M. Z. H., Ozeki, Y., Alamri, M. A., & Kawsar, S. M. A. (2024). Flavonoids as potential KRAS inhibitors: DFT, molecular docking, molecular dynamics simulation and ADMET analyses. Journal of Asian Natural Products Research, 26(8), 955–992. https://doi.org/10.1080/10286020.2024.2343821

Qi, J., Meng, M., Liu, J., Song, X., Chen, Y., Liu, Y., Li, X., Zhou, Z., Huang, X., Wang, X., Zhou, Q., & Zhao, Z. (2023). Lycorine inhibits pancreatic cancer cell growth and neovascularization by inducing Notch1 degradation and downregulating key vasculogenic genes. Biochemical Pharmacology, 217, 115833. https://doi.org/10.1016/j.bcp.2023.115833

Rahmi, N., & Hutagaol, H. (2025). Tinjauan Pustaka: Kanker Pankreas. Mutiara: Jurnal Penelitian dan Karya Ilmiah, 3(3), 297–308. https://doi.org/10.59059/mutiara.v3i3.2608

Shamsian, S., Sokouti, B., & Dastmalchi, S. (2024). Benchmarking different docking protocols for predicting the binding poses of ligands complexed with cyclooxygenase enzymes and screening chemical libraries. BioImpacts, 14(2), 29955. https://doi.org/10.34172/bi.2023.29955

Subramani, R., Gonzalez, E., Arumugam, A., Nandy, S., Gonzalez, V., Medel, J., Camacho, F., Ortega, A., Bonkoungou, S., Narayan, M., Dwivedi, A. K., & Lakshmanaswamy, R. (2016). Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition. Scientific Reports, 6, 19819. https://doi.org/10.1038/srep19819

Suyal, C., Shenoy, K. M., Kishore, A., & Kini, S. G. (2025). Structure–activity relationships of KRAS-G12D inhibitors for pancreatic cancer. Drug Discovery Today, 30(7), 104396. https://doi.org/10.1016/j.drudis.2025.104396

Tu, G., Gong, Y., Yao, X., Liu, Q., Xue, W., & Zhang, R. (2024). Pathways and mechanism of MRTX1133 binding to KRAS G12D elucidated by molecular dynamics simulations and Markov state models. International Journal of Biological Macromolecules, 274, 133374. https://doi.org/10.1016/j.ijbiomac.2024.133374

Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002). Molecular properties that influence the oral bioavailability of drug candidates. Journal of Medicinal Chemistry, 45(12), 2615–2623. https://doi.org/10.1021/jm020017n

Wang, X., Allen, S., Blake, J. F., Bowcut, V., Briere, D. M., Calinisan, A., Dahlke, J. R., Fell, J. B., Fischer, J. P., Gunn, R. J., Hallin, J., Laguer, J., Lawson, J. D., Medwid, J., Newhouse, B., Nguyen, P., O’Leary, J. M., Olson, P., Pajk, S., … Marx, M. A. (2022). Identification of MRTX1133, a noncovalent, potent, and selective KRASG12D inhibitor. Journal of Medicinal Chemistry, 65(4), 3123–3133. https://doi.org/10.1021/acs.jmedchem.1c01688

Zanger, U. M., & Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics, 138(1), 103–141. https://doi.org/10.1016/j.pharmthera.2012.12.007

Zhang, Z., Chen, W.-Q., Zhang, S.-Q., Bai, J.-X., Liu, B., Yung, K. K. L., & Ko, J. K. S. (2022). Isoliquiritigenin inhibits pancreatic cancer progression through blockade of p38 MAPK-regulated autophagy. Phytomedicine, 106, 154406. https://doi.org/10.1016/j.phymed.2022.154406