Pharmacophore modeling for the identification of small-molecule inhibitors of TACE

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 c...

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Main Authors: Liu, Li-Juan, Leung, Ka-Ho, Lin, Sheng, Chan, Daniel Shiu-Hin, Susanti, Dewi, Rao, Weidong, Chan, Philip Wai Hong, Ma, Dik-Lung, Leung, Chung-Hang
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2016
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Online Access:https://hdl.handle.net/10356/82167
http://hdl.handle.net/10220/41148
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-821672020-03-07T12:31:32Z Pharmacophore modeling for the identification of small-molecule inhibitors of TACE Liu, Li-Juan Leung, Ka-Ho Lin, Sheng Chan, Daniel Shiu-Hin Susanti, Dewi Rao, Weidong Chan, Philip Wai Hong Ma, Dik-Lung Leung, Chung-Hang School of Physical and Mathematical Sciences Pharmacophore TACE 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. ASTAR (Agency for Sci., Tech. and Research, S’pore) 2016-08-17T06:45:11Z 2019-12-06T14:47:54Z 2016-08-17T06:45:11Z 2019-12-06T14:47:54Z 2014 Journal Article 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. 1046-2023 https://hdl.handle.net/10356/82167 http://hdl.handle.net/10220/41148 10.1016/j.ymeth.2014.09.005 en Methods © 2014 Elsevier Inc.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic Pharmacophore
TACE
spellingShingle Pharmacophore
TACE
Liu, Li-Juan
Leung, Ka-Ho
Lin, Sheng
Chan, Daniel Shiu-Hin
Susanti, Dewi
Rao, Weidong
Chan, Philip Wai Hong
Ma, Dik-Lung
Leung, Chung-Hang
Pharmacophore modeling for the identification of small-molecule inhibitors of TACE
description 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.
author2 School of Physical and Mathematical Sciences
author_facet School of Physical and Mathematical Sciences
Liu, Li-Juan
Leung, Ka-Ho
Lin, Sheng
Chan, Daniel Shiu-Hin
Susanti, Dewi
Rao, Weidong
Chan, Philip Wai Hong
Ma, Dik-Lung
Leung, Chung-Hang
format Article
author Liu, Li-Juan
Leung, Ka-Ho
Lin, Sheng
Chan, Daniel Shiu-Hin
Susanti, Dewi
Rao, Weidong
Chan, Philip Wai Hong
Ma, Dik-Lung
Leung, Chung-Hang
author_sort Liu, Li-Juan
title Pharmacophore modeling for the identification of small-molecule inhibitors of TACE
title_short Pharmacophore modeling for the identification of small-molecule inhibitors of TACE
title_full Pharmacophore modeling for the identification of small-molecule inhibitors of TACE
title_fullStr Pharmacophore modeling for the identification of small-molecule inhibitors of TACE
title_full_unstemmed Pharmacophore modeling for the identification of small-molecule inhibitors of TACE
title_sort pharmacophore modeling for the identification of small-molecule inhibitors of tace
publishDate 2016
url https://hdl.handle.net/10356/82167
http://hdl.handle.net/10220/41148
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