Title:Unveiling the ESR1 Conformational Stability and Screening Potent
Inhibitors for Breast Cancer Treatment
Volume: 20
Issue: 3
Author(s): Khushboo Sharma, Umesh Panwar, Maddala Madhavi, Isha Joshi, Ishita Chopra, Lovely Soni, Arshiya Khan, Anushka Bhrdwaj, Abhyuday Singh Parihar, Vineeth Pazharathu Mohan, Leena Prajapati, Rashmi Sharma, Shweta Agrawal, Tajamul Hussain, Anuraj Nayarisseri*Sanjeev Kumar Singh
Affiliation:
- In silico Research Laboratory, Eminent Biosciences, 91, Sector A, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh,
India
- Computer Aided Drug Designing and Molecular Modelling Lab, Department of Bioinformatics, Alagappa
University, Karaikudi-630 003, Tamil Nadu, India
- Research Chair for Biomedical
Applications of Nanomaterials, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi
Arabia
- Bioinformatics Research Laboratory, LeGene Biosciences Pvt Ltd., Indore - 452010, Madhya Pradesh, India
Keywords:
Cancer, ESR1, Erα, virtual screening, docking based simulation, binding affinity, R programming.
Abstract:
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.
Methods: 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.
