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Pharmacophoric Site Identification and Inhibitor Design for Autotaxin.

ABSTRACT: 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.

SUBMITTER: Lee MH

PROVIDER: S-EPMC6696049 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Pharmacophoric Site Identification and Inhibitor Design for Autotaxin.

Lee Myeong Hwi MH Lee Dae-Yon DY Balupuri Anand A Jeong Jong-Woo JW Kang Nam Sook NS

Molecules (Basel, Switzerland) 20190801 15

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 biol ...[more]

PMID: 31374894

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