Author:
Kim Jin-Hee,Jeong Jin-Hyun
Abstract
Triple-negative breast cancer (TNBC) is defined as a kind of breast cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2). This cancer accounts for 10–15% of all breast cancers and has the features of high invasiveness and metastatic potential. The treatment regimens are still lacking and need to develop novel inhibitors for therapeutic strategies. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses, based on a series of forty-seven thieno-pyrimidine derivatives, were performed to identify the key structural features for the inhibitory biological activities. The established comparative molecular field analysis (CoMFA) presented a leave-one-out cross-validated correlation coefficient q2 of 0.818 and a determination coefficient r2 of 0.917. In comparative molecular similarity indices analysis (CoMSIA), a q2 of 0.801 and an r2 of 0.897 were exhibited. The predictive capability of these models was confirmed by using external validation and was further validated by the progressive scrambling stability test. From these results of validation, the models were determined to be statistically reliable and robust. This study could provide valuable information for further optimization and design of novel inhibitors against metastatic breast cancer.
Funder
National Research Foundation of Korea
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference35 articles.
1. Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants that Accelerate the Breast Cancer Pathways: A Computational Modelling Study;Front. Mol. Biosci.,2021
2. Incidence and Mortality and Epidemiology of Breast Cancer in the World;Asian Pac. J. Cancer Prev.,2016
3. (2021, March 26). World Health Organization. Available online: http://www.who.int/news-room/fact-sheets/detail/breast-cancer.
4. Medina, M.A., Oza, G., Sharma, A., Arriaga, L.G., Hernández, J.M.H., Rotello, V.M., and Ramirez, J.T. (2020). Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies. Int. J. Environ. Res. Public Health, 17.
5. Current Triple-Negative Breast Cancer Subtypes: Dissecting the Most Aggressive Form of Breast Cancer;Front. Oncol.,2021
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