Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume -, Issue -, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2023.2214209
Keywords
Breast cancer; NF-kappa B; structure-based 3D pharmacophore model; virtual screening; molecular docking; molecular dynamic simulation
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Breast cancer is a silent killer disease among women and a significant economic burden. Despite advances in research and treatment, breast cancer remains a growing ailment. This study aims to identify new drug targets for breast cancer by targeting specific proteins.
Breast cancer is a silent killer malady among women and a serious economic burden in health care management. A case of breast cancer is diagnosed among women every 19 s, and every 74 s, a woman dies of breast cancer somewhere in the world. Despite the pop-up of progressive research, advanced treatment approaches, and preventive measures, breast cancer remains amplifying ailment. The nuclear factor kappa B (NF-?B) is a key transcription factor that links inflammation with cancer and is demonstrated as being involved in the tumorigenesis of breast cancer. The NF-?B transcription factor family in mammals consists of five proteins; c-Rel, RelA(p65), RelB, NF-?B1(p50), and NF-?B2(p52). The antitumor effect of NF-?B has also been explored in breast cancer, however, the actual treatment for breast cancer is yet to be discovered. This study is attributed to the identification of novel drug targets against breast cancer by targeting c-Rel, RelA(p65), RelB, NF-?B1(p50), and NF-?B2(p52) proteins. To identify the putative active compounds, a structure-based 3D pharmacophore model to the protein active site cavity was generated followed by virtual screening, molecular docking, and molecular dynamics (MD) simulation. Initially, a library of 45000 compounds were docked against the target protein and five compounds namely Z56811101, Z653426226, Z1097341967, Z92743432, and Z464101066 were selected for further analysis. The relative binding affinity of Z56811101, Z653426226, Z1097341967, Z92743432, and Z464101066 with NF-?B1 (p50), NF-?B2 (p52), RelA (p65), RelB, and c-Rel proteins were -6.8, -8, -7.0, -6.9, and -7.2 kcal/mol, respectively which remained stable throughout the simulations of 200 ns. Furthermore, all of these compounds depict maximum drug-like properties. Therefore, the proposed compounds can be a potential candidate for patients with breast cancer, but, experimental validation is needed to ensure their safety.
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