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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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-08, Vol.24 (15), p.2808
Main Authors: Lee, Myeong Hwi, Lee, Dae-Yon, Balupuri, Anand, Jeong, Jong-Woo, Kang, Nam Sook
Format: Article
Language:English
Subjects:
Accuracy
autotaxin
Binding sites
Clinical trials
Computer applications
Design
Drug Design
Drug development
Humans
Hydrogen bonds
Inflammation - drug therapy
Inflammatory diseases
Kinases
Ligands
molecular docking
Molecular Docking Simulation
molecular dynamics simulation
Neoplasms - drug therapy
Pharmacology
Phosphodiesterase Inhibitors - chemistry
Phosphodiesterase Inhibitors - therapeutic use
Phosphoric Diester Hydrolases - chemistry
Phosphoric Diester Hydrolases - drug effects
Protein folding
Signal transduction
Structure-Activity Relationship
Therapeutic targets
topological water networks
Water - chemistry
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Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24152808