Unexpected emergence of luciferase-inhibitory activity during structural development study of phenyloxadiazole-based PPAR ligands

Ryuta Shioi, Yosuke Toyota, Tomomi Noguchi-Yachide, Minoru Ishikawa, Takao Yamaguchi, Makoto Makishima, Yuichi Hashimoto, Kenji Ohgane

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate transcription of genes involved in lipid, glucose, and cholesterol homeostasis in a ligand-dependent manner. PPARs have long been a target of drug development, and evaluation of PPARs activity frequently involves reporter-gene assay, in which luciferase activity is utilized to visualize transcriptional activation by the receptors. Here, we report our experience of the unexpected emergence of luciferase-inhibitory activity during our search for PPAR antagonists. We believe information about negative experiences like this will help to make medicinal chemists more aware of potential pitfalls in SAR studies with luciferase-based assays.

Original languageEnglish
Pages (from-to)854-864
Number of pages11
JournalHeterocycles
Volume97
Issue number2
DOIs
Publication statusPublished - 2018 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

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  • Cite this

    Shioi, R., Toyota, Y., Noguchi-Yachide, T., Ishikawa, M., Yamaguchi, T., Makishima, M., Hashimoto, Y., & Ohgane, K. (2018). Unexpected emergence of luciferase-inhibitory activity during structural development study of phenyloxadiazole-based PPAR ligands. Heterocycles, 97(2), 854-864. https://doi.org/10.3987/COM-18-S(T)61