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NAD(P)H: quinone oxidoreductase 1 (NQO1) is a ubiquitous flavoenzyme. NQO1 is important for catalyzation, detoxification, and reduction of organic compounds including quinone. Elevated NQO1 expression is associated with increased pancreatic ductal adenocarcinoma (PDAC) growth, and metastasis as well as poor prognosis. BBI 608 is a small molecule that exhibits potential therapeutic properties for PDAC due to its powerful anti-inflammatory and antioxidant properties and ability to regulate multiple signaling pathways. The current study explores the binding capacity and ligand efficacy of BBI608 against NQO1 in PDAC. To observe the molecular properties of BBI608 and to analyze the exact mechanism of NQO1 on PDAC, computational approaches were applied, including molecular docking. This investigation provides a detailed understanding of the interaction between NQO1 and BBI608 and its implication in PDAC therapy. To support this computational analysis, we performed in vitro and in vivo studies. The combination of BBI608 with gemcitabine plus irradiation creates higher cytotoxicity (decreased proliferation, clonogenicity and increased Annexin V positive cells; p Citation Format: Purnachandra N. Ganji, Gregory B. Lesinski, Bassel F. El-Rayes. Targeting NAD(P)H:quinone oxidoreductase 1 (NQO1) in pancreatic ductal adenocarcinoma: An in silco, in vitro and in vivo approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 104. |
