Unveiling the ESR1 Conformational Stability and Screening Potent Inhibitors for Breast Cancer Treatment

BACKGROUND: The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses. METHOD: In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα. RESULTS: Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity. CONCLUSION: Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer.

Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation of EGFR for the Clinical Treatment of Glioblastoma.

Glioblastoma (GBM) is a WHO Grade IV tumor with poor visibility, a high risk of comorbidity, and exhibit limited treatment options. Resurfacing from second-rate glioma was originally classified as either mandatory or optional. Recent interest in personalized medicine has motivated research toward biomarker stratification-based individualized illness therapy. GBM biomarkers have been investigated for their potential utility in prognostic stratification, driving the development of targeted therapy and customizing therapeutic treatment. Due to the availability of a specific EGFRvIII mutational variation with a clear function in glioma-genesis, recent research suggests that EGFR has the potential to be a prognostic factor in GBM, while others have shown no clinical link between EGFR and survival. The pre-existing pharmaceutical lapatinib (PubChem ID: 208,908) with a higher affinity score is used for virtual screening. As a result, the current study revealed a newly screened chemical (PubChem CID: 59,671,768) with a higher affinity than the previously known molecule. When the two compounds are compared, the former has the lowest re-rank score. The time-resolved features of a virtually screened chemical and an established compound were investigated using molecular dynamics simulation. Both compounds are equivalent, according to the ADMET study. This report implies that the virtual screened chemical could be a promising Glioblastoma therapy.