Pharmacophoric Site Identification and Inhibitor Design for Autotaxin

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Myeong Hwi LeeNam Sook Kang

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.

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Citations

Sep 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kristina KraljićMilan Mesić
Jul 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sandra Gemma
Sep 23, 2020·International Journal of Molecular Sciences·Hye Ree YoonNam Sook Kang
Nov 28, 2021·Pharmaceuticals·Yi JiaHai Shang

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Methods Mentioned

BETA
protein folding
column chromatography

Clinical Trials Mentioned

NCT02738801
NCT03143712
NCT02179502
NCT03515382
NCT03733444
NCT03711162

Software Mentioned

Grafit5
Discovery
GROMOS96
CHARMM

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