In Silico Study of Melinjo seeds (Gnetum gnemon L.) against Estrogen Receptor Alpha (ERα) in Breast Cancer

Abstract

Breast cancer is the second most common type of cancer worldwide, with a mortality rate reaching 666,103 deaths in 2022. The most frequently observed subtype of breast cancer is characterized by the expression of estrogen receptor alpha (ERα). Tamoxifen, an ERα antagonist, has long served as a first-line therapy for ER-positive breast cancer. Despite its clinical efficacy, issues related to toxicity and the potential development of resistance during long-term use remain significant limitations to its application. Melinjo (Gnetum gnemon L.) has been reported to contain bioactive compounds, such as stilbenoids and flavonoids, which exhibit promising anticancer properties. This study aims to evaluate the potential of bioactive compounds from Gnetum gnemon L. as a candidate for breast cancer therapy through drug-likeness prediction, pharmacokinetic profiling, and molecular docking against ERα. The results of this study identified Gnetin C as a promising lead compound, with a binding energy of –10.47 kcal/mol and an inhibition constant of 0.021 µM. These findings highlight the potential of Gnetin C for further development as a candidate therapeutic agent against breast cancer.