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

IF 1.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Pub Date : 2024-01-01 DOI:10.2174/0115734064256978231024062937

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

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引用次数: 0

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.

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揭示ESR1构象稳定性并筛选用于癌症治疗的有效抑制剂。

背景：目前的研究认识到雌激素受体α（ERα）作为核受体蛋白家族成员的重要性，该家族在癌症的病理生理学中起着核心作用。ERα是一种有价值的预后标志物，在预测疾病结果和治疗反应方面具有既定的相关性。方法：在本研究中，利用计算方法寻找合适的类药物化合物，这些化合物表现出与ERα类似的配体结合动力学。结果：基于对接的模拟筛选出了针对靶蛋白的前5个化合物——锌13377936、NCI35753、锌35465238、锌14726791和NCI663569。此外，他们的动力学研究表明，化合物锌13377936和NCI35753表现出最高的结合稳定性和亲和力。结论：由于预测了ERα蛋白在癌症中表达的竞争性抑制，我们认为锌13377936和NCI35753化合物都有望成为潜在的治疗剂。这些候选药物值得在临床试验的背景下进行严格的体外和体内评估。目前这项研究的结果对癌症未来诊断和治疗方法的发展具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medicinal Chemistry 医学-医药化学

CiteScore

4.30

自引率

4.30%

发文量

109

审稿时长

12 months

期刊介绍： Aims & Scope Medicinal Chemistry a peer-reviewed journal, aims to cover all the latest outstanding developments in medicinal chemistry and rational drug design. The journal publishes original research, mini-review articles and guest edited thematic issues covering recent research and developments in the field. Articles are published rapidly by taking full advantage of Internet technology for both the submission and peer review of manuscripts. Medicinal Chemistry is an essential journal for all involved in drug design and discovery.