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|Title:||Pharmacophore modeling for the identification of small-molecule inhibitors of TACE||Authors:||Liu, Li-Juan
Chan, Daniel Shiu-Hin
Chan, Philip Wai Hong
|Issue Date:||2014||Source:||Liu, L.-J., Leung, K.-H., Lin, S., Chan, D. S.-H., Susanti, D., Rao, W., et al. (2014). Pharmacophore modeling for the identification of small-molecule inhibitors of TACE. Methods, 71, 92-97.||Series/Report no.:||Methods||Abstract:||Tumor necrosis factor α-converting enzyme (TACE) plays a critical role in diverse physiological processes such as inflammation, hematopoiesis, and development. In this study, a pharmacophore model constructed from a training set of TACE inhibitors was used to screen an in-house database of organic compounds, from which compound 1 emerged as a top candidate. In a cell-free assay, compound 1 inhibited TACE enzymatic activity in a dose-dependent manner. Moreover, compound 1 inhibited the production of soluble TNF-α in human acute monocytic leukemia THP-1 cells without impacting nitric oxide production, and exhibited anti-proliferative activity against THP-1 cells. We envisage that compound 1 may be employed as a useful scaffold for the development of more potent TACE inhibitors. This study also validates the use of pharmacophore modeling to identify enzyme inhibitors.||URI:||https://hdl.handle.net/10356/82167
|ISSN:||1046-2023||DOI:||10.1016/j.ymeth.2014.09.005||Rights:||© 2014 Elsevier Inc.||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||SPMS Journal Articles|
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