Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Myeong Hwi, Lee, Dae-Yon, Balupuri, Anand, Jeong, Jong-Woo, Kang, Nam Sook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696049/
https://www.ncbi.nlm.nih.gov/pubmed/31374894
http://dx.doi.org/10.3390/molecules24152808
Descripción
Sumario: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.