STA-55, an Easily Accessible, Broad-Spectrum, Activity-Based Aldehyde Dehydrogenase Probe

Chembiochem. 2020 Jul 1;21(13):1911-1917. doi: 10.1002/cbic.201900771. Epub 2020 Feb 27.

Abstract

Aldehyde dehydrogenases (ALDHs) convert aldehydes into carboxylic acids and are often upregulated in cancer. They have been linked to therapy resistance and are therefore potential therapeutic targets. However, only a few selective and potent inhibitors are currently available for this group of enzymes. Competitive activity-based protein profiling (ABPP) would aid the development and validation of new selective inhibitors. Herein, a broad-spectrum activity-based probe that reports on several ALDHs is presented. This probe was used in a competitive ABPP protocol against three ALDH inhibitors in lung cancer cells to determine their selectivity profiles and establish their target engagement.

Keywords: activity-based protein profiling; aldehyde dehydrogenases; cancer; proteomics; target engagement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / antagonists & inhibitors
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism*
  • Cell Line, Tumor
  • Click Chemistry
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Fluorescent Dyes / chemistry
  • Humans
  • Proteomics

Substances

  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Aldehyde Dehydrogenase