Genistein as a Potential Breast Cancer Therapeutic: Computational Investigations Targeting EGFR and Oncogenic Pathways

Therapeutic Potential of Icariin in Breast Cancer: An Integrated Network Pharmacology and Molecular Simulations Approach

Findings support the hypothesis that ICA may serve as a valuable natural compound for treating HER2‐driven breast cancer; it requires further experimental validation.

Targeting EGFR in cancer using Terminalia arjuna: An integrated In Silico, molecular dynamics, experimental validation, and network pharmacology study.

The Epidermal Growth Factor Receptor (EGFR) plays a pivotal role in 20-60% of cancer cases, including glioblastoma, lung adenocarcinoma, and head and neck squamous cell carcinoma, as reported in The Cancer Genome Atlas (TCGA) dataset. The present study employed an integrated in silico and experimental workflow to evaluate EGFR-targeted compounds from Terminalia arjuna. Drug-likeness and ADMET screening were performed, followed by molecular docking and 1000 ns molecular dynamics simulations. In vitro validation was conducted using cancer cell-based assays and network pharmacology to explore the molecular mechanisms associated with the identified compound. Screening shortlisted eight compounds from T. arjuna. Molecular docking identified Arjunaside C (-8.2 kcal/mol), Arjunapthanoloside (-7.7 kcal/mol), and Beta-sitosterol (-7.4 kcal/mol) as potential EGFR inhibitors compared to Erlotinib (-6.6 kcal/mol). Arjunapthanoloside formed more H-bonds and exhibited most stable interactions with EGFR. MD simulations at 1000 ns revealed lower RMSD, RMSF, SASA, and Rg values for the Arjunapthanoloside-EGFR complex, indicating enhanced stability. Direct binding validation was limited by the unavailability of purified Arjunapthanoloside; therefore, Arjuna extract was evaluated, which demonstrated potent cytotoxicity with an IC₅₀ of 9 µg/mL in H357 oral cancer cells. Flow cytometry confirmed apoptosis-mediated cell death by increased early- and late-apoptotic cell populations. Network pharmacology analysis further identified additional targets (MMP3, MMP7, MMP9, and HRAS) that are directly involved in various cancers. Overall, the findings provide new insights into the therapeutic potential of Arjunapthanoloside as a stable compound that interacts with EGFR from T. arjuna, highlighting its significance in EGFR-targeted anticancer research.

Integrated Computational and Experimental Discovery of Antitumoral Peptides Targeting Luminal A and Triple-Negative Breast Cancer

The combined computational and experimental approach enabled the identification of peptides with selective cytotoxic effects and favorable predicted immunogenic profiles, demonstrating that integrating computational screening with experimental validation is an effective strategy for accelerating the discovery of selective anticancer peptides.

EGFR-Targeted Amino Quinoxaline Derivatives as Potential Anticancer Interventions: In Silico Design and in Vitro Evaluations

The Epidermal Growth Factor Receptor (EGFR) remains validated therapeutic goalfor Breast Cancer, especially because of its function in signalling pathways that promote tumor development and viability. In the current investigation, a series of newly designed amino quinoxaline derivatives (QN1–QN10) were investigated for their potential EGFR inhibitory and anticancer activities using an integrated in silico and in vitro approach. Molecular docking studies were carried out using Schrödinger Maestro to rate the binding kineticsof the designed compounds with the EGFR tyrosine kinase domain (PDB ID: 4HJO), employing erlotinib as the reference standard. The docking protocol was validated by redockingerlotinib into the active site, confirming the reliability of the methodology. Glide extra-precision (XP) docking revealed favourable binding orientations of selected derivatives within the EGFR catalytic pocket. The cytotoxicity of selected compounds (QN2, QN4, and QN8) was further calculated through MTT assay for human breast cancer cell line MCF-7. The results proved that the cell longevity was decreased in a concentration-dependent way, with erlotinib exhibiting the greatest potency (LC50 = 18.47 µg/mL). Among the synthesized derivatives, QN4 showed relatively higher activity (LC50 = 121.52 µg/mL) than QN2 and QN8.Statistical analysis proved the relevance of the cytotoxic effects observed (p < 0.0001). Overall, the combined computational and biological findings suggest that amino quinoxaline scaffolds indicate potential avenues for enhanced optimization as EGFR-targeted anticancer drugs.

Structure-guided identification and experimental validation of NAT10-targeting small molecules in colorectal cancer cells

Computational identification and evaluation of Adenium obesum phytochemicals as potential EGFR inhibitors for targeted therapy against non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) remains the leading cause of lung cancer–related mortality, largely driven by aberrant activation of the epidermal growth factor receptor (EGFR). Despite the clinical success of EGFR tyrosine kinase inhibitors (TKIs), intrinsic and acquired resistance, coupled with safety concerns, highlight the need for novel, safer inhibitors. Natural products represent an underexplored source of structurally diverse bioactive compounds with favorable biocompatibility. In this study, a comprehensive in silico approach is used to evaluate phytochemicals from Adenium obesum as potential candidate EGFR-targeting compound. Initially, sixteen phytochemicals were first assessed for predicted antineoplastic activity using PASS. High-scoring molecules were docked against the EGFR kinase domain (PDB ID: 1M17), besides performed detailed protein–ligand interaction analysis, drug-likeness and ADMET profiling, toxicity prediction and 100-ns molecular dynamics (MD) simulations. PASS-based bioactivity prediction revealed strong anticancer potential among the sixteen screened compounds, with consistently high antineoplastic and antiproliferative activity probabilities (Pa > 0.79) and low inactivity scores, supporting their selection for subsequent docking, ADMET, and molecular dynamics analyses. Next, several phytochemicals exhibited strong docking affinities, with Cardenolide achieving the highest binding score (–9.9 kcal/mol) and forming stable interactions with key catalytic residues. A 100-ns MD simulation confirmed the structural stability, persistent binding, and dynamic integrity of the EGFR–Cardenolide complex under physiological conditions. Importantly, interaction mapping revealed that Cardenolide engages conserved and functionally critical regions of the EGFR kinase domain associated with catalytic activity and structural stability, supporting its mechanistic relevance as an ATP-competitive scaffold. Additionally, predicted pharmacokinetic and toxicity profiles further supported Cardenolide’s suitability as a drug-like candidate. Collectively, these results identify Cardenolide as a computationally prioritized candidate with favorable predicted EGFR-binding characteristics, structural stability, and physicochemical and toxicity profiles. However, as the present study is based entirely on computational analyses, these findings should be considered hypothesis-generating and do not establish EGFR inhibitory activity or therapeutic efficacy. Experimental validation, including biochemical kinase inhibition and cellular assays, is therefore required to determine the actual EGFR inhibitory potential and anticancer activity of Cardenolide. Nevertheless, the findings provide a rational basis for prioritizing Cardenolide for further experimental investigation and illustrate the potential of Adenium obesum phytochemicals as a source of candidate EGFR-targeting compounds for future NSCLC drug discovery.