In vitro benchmarking of NF-κB inhibitors

Eur J Pharmacol. 2020 Apr 15;873:172981. doi: 10.1016/j.ejphar.2020.172981. Epub 2020 Jan 31.

Abstract

Dysregulated activity of the transcription factors of the nuclear factor κb (NF-κB) family has been implicated in numerous cancer types, inflammatory diseases, autoimmune disease, and other disorders. As such, selective NF-κB pathway inhibition is an attractive target to researchers for preclinical and clinical drug development. A plethora of commercially and clinically available inhibitors claim to be NF-κB specific; however, such claims of specificity are rarely quantitative or benchmarked, making the biomedical literature difficult to contextualize. This imprecision is worsened because some NF-κB reporter systems have low signal-to-noise ratios. Herein, we use a robust, defined, commercially available reporter system to benchmark NF-κB agonists and antagonists for the field. We also functionally characterize a RELA fusion-positive ependymoma cell culture with validated NF-κB inhibitor compounds.

Keywords: Ependymoma; NF-κB; RELA.

MeSH terms

  • Benchmarking
  • Cell Fusion
  • Cell Line, Tumor
  • Cell Survival
  • Ependymoma / pathology
  • HEK293 Cells
  • Humans
  • In Vitro Techniques
  • NF-kappa B / agonists*
  • NF-kappa B / antagonists & inhibitors*
  • Reproducibility of Results
  • Signal-To-Noise Ratio

Substances

  • NF-kappa B