High-throughput, cell-based screens to identify small-molecule inhibitors of ricin toxin and related category b ribosome inactivating proteins (RIPs).

High-throughput, cell-based screens to identify small-molecule inhibitors of ricin toxin and related category b ribosome inactivating proteins (RIPs). Curr Protoc Toxicol. 2013 Feb;Chapter 2:Unit 2.23 Authors: Wahome PG, Mantis NJ 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. PMID: 23408195 [PubMed - indexed for MEDLINE]
Source: Current Protocols in Toxicology - Category: Toxicology Tags: Curr Protoc Toxicol Source Type: research