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

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

doi:10.2174/0115734064256978231024062937

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

Med Chem. 2023 Oct 27. doi: 10.2174/0115734064256978231024062937. Online ahead of print.

Authors

Khushboo Sharma^{1

2}, Umesh Panwar², Maddala Madhavi³, Isha Joshi¹, Ishita Chopra^{1

4}, Lovely Soni¹, Arshiya Khan^{1

2}, Anushka Bhrdwaj^{1

2}, Abhyuday Singh Parihar¹, Vineeth Pazharathu Mohan^{1

5}, Leena Prajapati¹, Rashmi Sharma¹, Shweta Agrawal¹, Tajamul Hussain^{6

7}, Anuraj Nayarisseri^{1

2

8

6}, Sanjeev Kumar Singh²

Affiliations

¹ In silico Research Laboratory, Eminent Biosciences, 91, Sector A, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, India
² Computer Aided Drug Designing and Molecular Modelling Lab, Department of Bioinformatics, Alagappa University, Karaikudi-630 003, Tamil Nadu, India
³ Department of Zoology, Osmania University, Hyderabad - 500007, Telangana State, India
⁴ School of Medicine and Health Sciences, The George Washington University, Ross Hall, 2300 Eye Street, NW Washington, D.C. - 20037, USA
⁵ Department of Biosciences, School of Science and Technology, Nottingham Trent University Clifton Campus, Nottingham, NG11 8NS, United Kingdom
⁶ Research Chair for Biomedical Applications of Nanomaterials, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
⁷ Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia
⁸ Bioinformatics Research Laboratory, LeGene Biosciences Pvt Ltd., Indore - 452010, Madhya Pradesh, India

PMID: 37929724
DOI: 10.2174/0115734064256978231024062937

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.

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.

Keywords: Cancer; ESR1; Erα; R programming.; binding affinity; docking based simulation; virtual screening.