A small-molecule screen identifies the antitrypanosomal agent suramin and analogues NF023 and NF449 as inhibitors of STAT5a/b.

Abstract

The transcription factor STAT5a is a potential target for tumor therapy. We present a fluorescence polarization-based, high-throughput screen of chemical libraries containing natural products and known bioactive molecules, for the identification of small-molecule inhibitors of the STAT5a SH2 domain. This screen identified suramin, a drug used to treat African trypanosomiasis, and its analogues NF023 and NF449 as inhibitors of the SH2 domains of STAT5a/b. Our data extend the known in vitro targets of suramin and analogues to include members of the STAT protein family.

• Authors: Angela Berg, Thorsten Berg
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 27 Issue 15 Pg. 3349-3352 (08 01 2017) ISSN: 1464-3405 [Electronic] England
• PMID: 28624143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• 4,4,',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis(benzene-1,3-disulfonate)
• Benzenesulfonates
• STAT5 Transcription Factor
• STAT5A protein, human
• STAT5B protein, human
• Small Molecule Libraries
• Tumor Suppressor Proteins
• Suramin

Topics

• Benzenesulfonates (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• High-Throughput Screening Assays
• Humans
• Molecular Structure
• STAT5 Transcription Factor (antagonists & inhibitors)
• Small Molecule Libraries (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Suramin (analogs & derivatives, chemical synthesis, pharmacology)
• Tumor Suppressor Proteins (antagonists & inhibitors)