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This study aims to identify non-toxic inhibitors targeting the HER-2 receptor in breast cancer using molecular docking.

June 2, 2026Open Access

Screening and docking molecular studies of natural products targeting overexpressed receptors HER-2 in breast cancer

Key Points

This study aims to identify non-toxic inhibitors targeting the HER-2 receptor in breast cancer using molecular docking.
Conducted virtual screening of 102 ligands from natural and dietary compounds.
Focused on molecular docking to assess binding affinities (DeltaG) to the HER-2 receptor.
Identified 23 promising compounds for further in vitro/in vivo testing.
Lycopene showed the strongest binding affinity with DeltaG of -9.82 kcal/mol.
Luteolin, Anacardic acid, and alpha-Tocopherol demonstrated significant inhibitory effects along key residues.
Natural products showed comparable or stronger binding to HER-2 than Lapatinib, with potential to replace current chemotherapies.

Abstract

The first cancer to strike a community is breast cancer. Because of its extremely high mitotic activity, breast cancer that tests positive for HER 2 is thought to have a bad prognosis. Due to the effects caused by chemical drugs, patients are increasingly turning to natural medicine, such as phytotherapy and nutritherapy. The main objective of this study is to search, using a bioinformatics approach (molecular docking), for new non-toxic anti-cancer inhibitors by carrying out a screening of 102 ligands from natural and dietary compounds, likely to interact with the HER-2.The results of the virtual screening permit to choose 23 best compounds which can be proposed as the best inhibitors of HER-2. Lycopene would be a very promising ligand which presents a DeltaG of -9.82 kcal/mol, followed by Beta-carotene (DeltaG of -8.58), P-cumaric acid kcal/mol (DeltaG of -8.57) and Curcumin (DeltaG of -8.46). Another compounds; luteolin, anacardium (Anacardic acid) and alpha-Tocopherol were found to have the strongest inhibitory effects, with DeltaG values of -7.92 kcal/mol, -7.89 kcal/mol and-7.85 kcal/mol, respectively, and act directly on residues keys found in the hydrophobic pocket II (ATP binding site) and the hydrophobic region (the αC-β4 loop) of the EGFR domain. Pinoresino, Kaempferol and Caffeic acid with DeltaGs of -7.48 Kcal/mol, -6.88 Kcal/mol and -6.34 kcal/mol, and are three ligands specific to the conserved regions of the HER-2 receptor and interact with the tail respectively; C-terminal, the C-lobe activation loop and the N-lobe P loop of the tyrosine kinase domain. The comparison of Lapatinib (chemical compound) and quercetin (natural compound) have respectively DeltaG of -7.58 kcal/mol and -7.28 kcal/mol, form a hydrogen bond with the same residue of the hydrophobic region. All the natural molecules seem very promising and, after in vitro/in vivo tests, could constitute good substitutes for the chemotherapies currently used to treat breast cancers as well as other cancers.

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