Development of novel silanol-based human pregnane X receptor (PXR) agonists with improved receptor selectivity

Hirozumi Toyama, Hitoshi Shirakawa, Michio Komai, Yuichi Hashimoto, Shinya Fujii

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Pregnane X receptor (PXR) is a ligand-dependent transcription factor that is considered to be a potential therapeutic target for multiple diseases. Herein, we report the development and structure-activity relationship studies of a new series of hPXR agonists. Focusing on our recently developed silanol-sulfonamide scaffold, we developed the potent hPXR agonist 28, which shows good selectivity over hLXRα and β, hFXR, and hRORα and γ. Examination of the structure-activity relationship suggested a possible strategy to manipulate the selectivity. Docking simulation indicated the presence of an additional binding cavity and polar contacts in the ligand-binding pocket of hPXR. This information should be helpful for the future development of more potent and selective hPXR ligands.

Original languageEnglish
Pages (from-to)4493-4501
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number15
Publication statusPublished - 2018 Aug 15


  • Alcohol/silanol-exchange
  • C/Si-exchange
  • Nuclear receptor
  • Pregnane X receptor
  • Sila-substitution
  • Silanol
  • T0901317

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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