A Small Molecule Inhibits Protein Disulfide Isomerase and Triggers the Chemosensitization of Cancer Cells1. Issue 47 (26th September 2014)

• Record Type: Journal Article
• Authors: Eirich, Jürgen; Braig, Simone; Schyschka, Liliana; Servatius, Phil; Hoffmann, Judith; Hecht, Sabrina; Fulda, Simone; Zahler, Stefan; Antes, Iris; Kazmaier, Uli; Sieber, Stephan A.; Vollmar, Angelika M.
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 47(2014)
• Page Start: 12960
• Page End: 12965
• Publication Date: 2014-09-26
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201406577
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Resistance to chemotherapeutic agents represents a major challenge in cancer research. One approach to this problem is combination therapy, the application of a toxic chemotherapeutic drug together with a sensitizing compound that addresses the vulnerability of cancer cells to induce apoptosis. Here we report the discovery of a new compound class (<bold>T8</bold>) that sensitizes various cancer cells towards etoposide treatment at subtoxic concentrations. Proteomic analysis revealed protein disulfide isomerase (PDI) as the target of the <bold>T8</bold> class. In‐depth chemical and biological studies such as the synthesis of optimized compounds, molecular docking analyses, cellular imaging, and apoptosis assays confirmed the unique mode of action through reversible PDI inhibition.</p> </abstract>