<![CDATA[Cancer is characterized by uncontrolled cell growth and proliferation, often progressing to invasion and metastasis. Among the signaling cascades driving this process, the PI3K/AKT/mTOR pathway plays a central role in regulating cell survival, proliferation, and apoptosis, with the AKT1 isoform frequently implicated in oncogenic transformation through gain-of-function mutations and aberrant activation. This study evaluated the anticancer potential of bioactive compounds from Kaempferia angustifolia Rosc. (kunci pepet) as AKT1 inhibitor candidates through an integrated in silico approach, encompassing Lipinski's Rule of Five, ADMETox prediction, pharmacophore screening, and molecular docking against the AKT1 receptor. Thirty structurally diverse compounds, representing multiple secondary metabolite classes, were selected to examine how structural variation influences AKT1 binding; twenty-nine were successfully evaluated through molecular docking. Nine compounds, including flavokawain A, alpinetin, zeylenol, α-cyperone, crotepoxide, kaempferol, sandaracopimaradiene, β-sitosterol, and eleutherin, emerged as promising candidates based on favorable drug-likeness, safety profiles, and binding characteristics. Among these, zeylenol achieved the highest pharmacophore fit score (40.11) and a binding energy (−8.37 kcal/mol) surpassing the native ligand, while kaempferol showed comparable docking performance. These findings position zeylenol as the most promising AKT1 inhibitor candidate from K. angustifolia, warranting further experimental validation for anticancer drug development.]]>
