UNIT 2.23 High-Throughput, Cell-Based Screens to Identify Small-Molecule Inhibitors of Ricin Toxin and Related Category B Ribosome Inactivating Proteins (RIPs)
Published Online: 1 FEB 2013
Copyright © 2013 by John Wiley & Sons, Inc.
Lab Protocol Title
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.
- Published Online: 1 FEB 2013
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.
- drug discovery;