Cell-Based Screening Systems for Developing Novel Insecticides: Insights from the EcR-Reporter Paradigm

Abstract

For the discovery of new insecticides, there is an increasing interest in the development of in vitro methods to replace conventional insect toxicity tests. The ultimate goal is to achieve an alternative system that allows for rapid (“high-throughput”) testing of candidate compounds enabling prediction of their efficacy at the whole animal level. Besides a dramatic increase in the number of compounds that can be screened, requirements for successful in vitro screening systems include reproducibility, predictive power for toxicity in vivo, and low cost/benefit ratio.

Here we present some relevant examples in the development of screening systems for discovery of biorational insecticides. The significant advances in ecdysone receptor (EcR)-based reporter systems are used as a paradigm to illustrate advantages and pitfalls of cell-based screening systems. While the EcR-based reporter assay can predict the hormonal activity of compounds accurately, unexpectedly, rather low predictive power exists whether such compounds with high activity in vitro can be developed and used as effective insecticides. Furthermore, the principles that guide effective insecticide activity for EcR agonists in larvae may differ among different insect groups. Thus, while in vitro systems can narrow down the number of compounds considerably, larvicidal assays at considerable scale remain necessary to assess efficacy.

The chapter concludes with a short presentation of two other applications of the EcR-reporter system: the identification of ecdysone antagonists and the testing of environmental compounds with endocrine disruptor activity.