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Screen natural terpenoids to identify potential Jab1 inhibitors for treating breast cancer

Pratibha Pandey
Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, India
Fahad Khan
Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, India
Kiran Yadav
Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, India
Kartikey Singh
Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, India
Akhlakur Rehman
Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, India
Avijit Mazumder
Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India.
Minhaj Ahmad Khan
Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Panjab, India
Received: 05 September 2024
Published: 29 June 2023

Abstract

Jab1 (c-Jun activation domain-binding protein-1) overexpression has been extensively linked to cancer development (or metastasis) in various malignancies by positively regulating cancer cell proliferation or inactivating several tumor suppressors. Recent research has focused on utilizing plant products to target crucial elements of dysregulated signaling pathways to elucidate a potent cancer therapeutic approach. Terpenoids have shown significant anti-inflammatory and anti-cancerous properties in a broader range of carcinomas by inducing apoptosis. Through an extensive literature search, we have selected only those terpenoids (from the NPACT database) that have not been explored against Jab1 (CSN5, COP9 signalosome subunit 5) in breast cancer for our research study. We have used two docking servers, PATCH DOCK, and CB DOCK, to find the binding interaction between selected terpenoids and Jab1. Further, we have also used SWISS ADME to investigate the pharmacokinetics of selected ligands. Amongst all selected ligands, lutein (belongs to the xanthophylls class) has displayed maximum binding energy in both CB Dock and Patch Dock analysis. Hence, our preliminary in silico results have shown lutein as the potent lead candidate for developing a better drug against breast cancer. However, more in silico and in vitro studies are still needed to validate the inhibitory potential of lutein terpenoid against Jab1 in breast cancer.

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