Innovation in insecticide discovery: Approaches to the discovery of new classes of insecticides

Abstract

The continuing demand for agrochemical insecticides that can meet increasing grower, environmental, consumer and regulatory requirements creates the need for the development of new solutions for managing crop pest insects. The development of resistance to the currently available insecticidal products adds another critical driver for new insecticidal active ingredients (AIs). One avenue to meeting these challenges is the creation of new classes of insecticidal molecules to act as starting points and prototypes stimulating further spectrum, efficacy and environmental impact refinements. A new class of insecticides is foreshadowed by the first molecule exemplifying that class (first‐in‐class, FIC) and offers one measure of innovation within the agrochemical industry. Most insecticides owe their discovery to competitor‐inspired (i.e. competitor patents/products) or next‐generation (follow‐on to a company's pre‐existing product) strategies. In contrast, FIC insecticides primarily emerge from a bioactive hypothesis approach, with the largest segment resulting from the exploration of new areas of chemistry/heterocycles and underexploited motifs. Natural products also play an important role in the discovery of FIC insecticides. Understanding the origins of these FIC compounds and the approaches used in their discovery can provide insights into successful strategies for future FIC insecticides. This review analyses information on historic and recently introduced FIC insecticides. Its main objective has been to identify the most successful discovery strategies for identifying new agrochemical solutions to meet the challenge of minimizing crop losses resulting from insects. © 2022 Society of Chemical Industry.

Natural Product-Based Crop Protection Compounds─Origins and Future Prospects

“…Altogether, 17% of crop protection AIs have a direct NP-based origin (Figure A), and for insecticides, the impact is even larger (ca. 30%; Figure B). , However, the impact of NPs on the discovery of new crop protection compounds is potentially far larger (ca. 50% of all crop protection AIs) when synthetic compounds are included that by chance happen to have a NP model that hypothetically could have led to their discovery (NPSE) (Figure A). ,, This hypothetical impact is again even larger for insecticides, for which nearly 75% of all of the insecticide AIs could potentially/hypothetically be linked to a NP. ,, …”

“…Natural products (NPs) have long been an key area of interest in the discovery of new crop protection AIs, ,− representing one of the most common approaches employed by research and development (R&D)-based companies involved in the discovery of new crop protection pesticide AIs (Figure ). ,,,,, A variety of companies, universities, and other institutions continue to explore known NPs and the search for new NPs that can serve as products or models for new crop protection compounds. ,,− ,− As highlighted by the example of insecticides, 75% of all commercial insecticides owe their discovery to a pre-existing molecule or model compound from a competitor (competitor inspired) or an earlier product within a company (next generation) . Thus, the first members of a new class of crop protection chemistry [i.e., first in class (FIC)] , are critical starting points to expand the breath of crop protection AI options.…”

Pesticide Research and Development: General Discussion and Spinosad Case

“…Innovative approaches to discover new classes of pesticides have been well-documented. 13 To be innovative, however, one may have to technically modify published methods to fit the needs of the internal program when necessary. For example, the half-maximum lethal dose (LD 50 ) measurement with mosquito larvae (Aedes aegypti) was a commonly used assay in laboratories to evaluate the biological activity of potential insecticides.…”

“…For insecticides, a successful test must be sensitive enough to pick up a chemical having reasonable activities (e.g., 10 ppm), able to manage a large number of samples (e.g., 100 samples daily), and have a quick turnaround time (e.g., 24 h). Innovative approaches to discover new classes of pesticides have been well-documented . To be innovative, however, one may have to technically modify published methods to fit the needs of the internal program when necessary.…”

Changes Are in the Air

“…Sparks and Bryant contributed two papers. The first was a perspective on the impact of natural compounds on discovery of pesticides (12), and the other covered innovation in insecticide discovery, with emphasis on new classes of insecticides (13). Gressel provides a thought‐provoking perspective on adapting a new technology to prevent binding of protein pesticide target subunits in order to develop a new type of pesticide with new molecular targets (14).…”