Unit

UNIT 2.23 High-Throughput, Cell-Based Screens to Identify Small-Molecule Inhibitors of Ricin Toxin and Related Category B Ribosome Inactivating Proteins (RIPs)

  1. Paul G. Wahome1,
  2. Nicholas J. Mantis1,2

Published Online: 1 FEB 2013

DOI: 10.1002/0471140856.tx0223s55

Current Protocols in Toxicology

Current Protocols in Toxicology

How to Cite

Wahome, P. G. and Mantis, N. J. 2013. High-Throughput, Cell-Based Screens to Identify Small-Molecule Inhibitors of Ricin Toxin and Related Category B Ribosome Inactivating Proteins (RIPs). Current Protocols in Toxicology. 55:2.23:2.23.1–2.23.14.

Author Information

  1. 1

    Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York

  2. 2

    Department of Biomedical Sciences, University at Albany School of Public Health, Albany, New York

Publication History

  1. Published Online: 1 FEB 2013

Abstract

Ricin is a member of the ubiquitous ribosome-inactivating protein (RIP) family of toxins. The Centers for Disease Control and Prevention (CDC) classify ricin and related toxins as Category B biothreat agents. There are currently no antidotes or therapeutics to counteract RIPs in humans. The discovery of effective small-molecule inhibitors of RIPs is increasingly possible, however, due to the availability and accessibility of diverse small-molecule chemical libraries coupled with robust robotics and automated screening methodologies. In this article, we describe a cell-based, high-throughput screening strategy and secondary assays that we have successfully used to identify compounds that target ricin toxin's enzymatic activity and intracellular trafficking, as well as stress-activated signaling pathways associated with cell death. The methods described in the protocol are amenable to the other RIPs. Curr. Protoc. Toxicol. 55:2.23.1-2.23.14. © 2013 by John Wiley & Sons, Inc.

Keywords:

  • drug discovery;
  • small-molecules;
  • high-throughput;
  • toxins;
  • biodefense