Pharmacophoric Site Identification and Inhibitor Design for Autotaxin

Pharmacophoric Site Identification and Inhibitor Design for Autotaxin

Autotaxin (ATX) is a potential drug target that is associated with inflammatory diseases and various cancers. In our previous studies, we have designed several inhibitors targeting ATX using computational and experimental approaches. Here, we have analyzed topological water networks (TWNs) in the bi...

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Main Authors: Myeong Hwi Lee, Dae-Yon Lee, Anand Balupuri, Jong-Woo Jeong, Nam Sook Kang
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Molecules
Subjects:
autotaxin
topological water networks
molecular docking
molecular dynamics simulation
Online Access:https://www.mdpi.com/1420-3049/24/15/2808
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spelling doaj-a2a6fc6e612840dc8ff00229370cb6dd2020-11-25T00:55:17ZengMDPI AGMolecules1420-30492019-08-012415280810.3390/molecules24152808molecules24152808Pharmacophoric Site Identification and Inhibitor Design for AutotaxinMyeong Hwi Lee0Dae-Yon Lee1Anand Balupuri2Jong-Woo Jeong3Nam Sook Kang4Graduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaLegoChem Biosciences, Inc., 8-26 Munoyeongseo-ro, Daedeok-gu, Daejeon 34302, KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaAutotaxin (ATX) is a potential drug target that is associated with inflammatory diseases and various cancers. In our previous studies, we have designed several inhibitors targeting ATX using computational and experimental approaches. Here, we have analyzed topological water networks (TWNs) in the binding pocket of ATX. TWN analysis revealed a pharmacophoric site inside the pocket. We designed and synthesized compounds considering the identified pharmacophoric site. Furthermore, we performed biological experiments to determine their ATX inhibitory activities. High potency of the designed compounds supports the predictions of the TWN analysis.https://www.mdpi.com/1420-3049/24/15/2808autotaxintopological water networksmolecular dockingmolecular dynamics simulation
collection DOAJ
language English
format Article
sources DOAJ
author Myeong Hwi Lee
Dae-Yon Lee
Anand Balupuri
Jong-Woo Jeong
Nam Sook Kang
spellingShingle Myeong Hwi Lee
Dae-Yon Lee
Anand Balupuri
Jong-Woo Jeong
Nam Sook Kang
Pharmacophoric Site Identification and Inhibitor Design for Autotaxin
Molecules
autotaxin
topological water networks
molecular docking
molecular dynamics simulation
author_facet Myeong Hwi Lee
Dae-Yon Lee
Anand Balupuri
Jong-Woo Jeong
Nam Sook Kang
author_sort Myeong Hwi Lee
title Pharmacophoric Site Identification and Inhibitor Design for Autotaxin
title_short Pharmacophoric Site Identification and Inhibitor Design for Autotaxin
title_full Pharmacophoric Site Identification and Inhibitor Design for Autotaxin
title_fullStr Pharmacophoric Site Identification and Inhibitor Design for Autotaxin
title_full_unstemmed Pharmacophoric Site Identification and Inhibitor Design for Autotaxin
title_sort pharmacophoric site identification and inhibitor design for autotaxin
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2019-08-01
description Autotaxin (ATX) is a potential drug target that is associated with inflammatory diseases and various cancers. In our previous studies, we have designed several inhibitors targeting ATX using computational and experimental approaches. Here, we have analyzed topological water networks (TWNs) in the binding pocket of ATX. TWN analysis revealed a pharmacophoric site inside the pocket. We designed and synthesized compounds considering the identified pharmacophoric site. Furthermore, we performed biological experiments to determine their ATX inhibitory activities. High potency of the designed compounds supports the predictions of the TWN analysis.
topic autotaxin
topological water networks
molecular docking
molecular dynamics simulation
url https://www.mdpi.com/1420-3049/24/15/2808
work_keys_str_mv AT myeonghwilee pharmacophoricsiteidentificationandinhibitordesignforautotaxin
AT daeyonlee pharmacophoricsiteidentificationandinhibitordesignforautotaxin
AT anandbalupuri pharmacophoricsiteidentificationandinhibitordesignforautotaxin
AT jongwoojeong pharmacophoricsiteidentificationandinhibitordesignforautotaxin
AT namsookkang pharmacophoricsiteidentificationandinhibitordesignforautotaxin
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