Discovery of Estrogen Receptor Alpha (ER-α) Inhibitors by In Silico

5th International Eurasian Conference on Biological and Chemical Sciences, Ankara, Türkiye, 23 - 25 Kasım 2022, ss.1620, (Özet Bildiri)

Abstract

Breast cancer stands out among all cancer types because it covers 15% of all cancer-related deaths and is diagnosed

frequently. Breast cancer occurs when exposed to many endogenous and exogenous factors, and this type of cancer has a

hereditary feature for the human body. Estrogen receptors are a nuclear hormone receptor that plays a role in the

development and control of the female reproductive system, also it considered as a good potential target in the control

and treatment of breast cancer cases. ER-α is a group of estrogen receptors and has been proven to be the main factor in

almost 65% of breast cancer cases. There is a need to develop new small molecules that modulate ER-α due to the

resistance and side effects that develop against current breast cancer treatment [1]. To meet this need, in this study, a

virtual screening was performed to determine the most affinity for the ER-α receptor among 900 compounds with a

benzothiophene skeleton. In this screening, ER-α crystal structure in complex with 4-hydroxytamoxifen ligand (PDB

code: 3ERT) was preferred as receptor protein and the complex structure was prepared using Schrödinger Protein

Preparation Wizard [2]. The ligand in the prepared structure was determined as the binding site. In addition, the library

with the benzothiophene skeleton (900 compounds) was created and their 3D structures were prepared with the LigPrep

module. Next, virtual screening was performed using Glide docking modules. Three compounds with the lowest Glide

XP score were identified as hit inhibitors as a result of the virtual screening. In conclusion, these three hit compounds

with benzothiophene skeleton could be new and effective anticancer drugs for breast cancer.

Keywords: ER-α, Virtual Screening, Benzothiophene

Acknowledgement: This work was funded by Ataturk University the Coordination Unit of Scientific Research Projects

(Project number FLP-2021-9543).

References:

[1] Kumar, N., Gulati, H. K., Sharma, A., Heer, S., Jassal, A. K., Arora, L., ... & Bedi, P. M. S. (2021). Most recent

strategies targeting estrogen receptor alpha for the treatment of breast cancer. Molecular Diversity, 25(1), 603-624.

[2] Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard, D. A., & Greene, G. L. (1998). The structural

basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell, 95(7), 927-

937.