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

ChemBioChem, vol. 21, pp. 1911–1917

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.

Authors 6

1. Sebastiaan T. A. Koenders Aachen Department of Molecular Physiology

   Leiden University

   Affiliation as printed

   Department of Molecular Physiology Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

2. Eva J. van Rooden Aachen Department of Molecular Physiology

   Leiden University

   Affiliation as printed

   Department of Molecular Physiology Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

3. Hans van den Elst Aachen Department of Bio-organic Synthesis

   Leiden University

   Affiliation as printed

   Department of Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Department of Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

4. Bogdan I. Florea Aachen Department of Bio-organic Synthesis

   Leiden University

   Affiliation as printed

   Department of Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Department of Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

5. Herman S. Overkleeft Aachen Department of Bio-organic Synthesis

   Leiden University

   Affiliation as printed

   Department of Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Department of Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

6. Mario van der Stelt corresponding Aachen Department of Molecular Physiology

   Leiden University

   Affiliation as printed

   Department of Molecular Physiology Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands