title: It takes a team: reflections on insecticide discoveries, toxicological problems and enjoying the unexpected.
abstract: Absorption/distribution/metabolism/excretion (ADME)-related studies are mandatory in agrochemical development/registration, but can also play a valuable role in the discovery process. In combination with target-site potency, bioavailability/ADME characteristics determine agrochemical bioactivity and selectivity, and these concerns can dictate the fate of a discovery lead area. Bioavailability/ADME research was critical to the eventual commercialization of three different insecticide chemistries examined in this paper. In one situation, improved systemicity in anthranilic diamides was required to expand pest spectrum. In another, ADME tools were needed to improve the selective toxicity and non-target safety of sodium channel blocker insecticides. Finally, differential ADME characteristics of two classes of hormone agonists dictated differential insecticidal activity, and were useful in optimizing the dibenzoylhydrazine ecdysone agonists. ADME discovery research will help companies to advance novel, efficacious and selective agrochemicals, but organizational patience and a desire to understand lead areas in depth are required. © 2016 Society of Chemical Industry.
authors.affiliation: Keith D Wing Consulting, LLC, Wilmington, DE, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wing
mesh_terms: D065567:Absorption, Physiological; D000818:Animals; D007301:Insect Hormones / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D007313:Insecta / Q000187:drug effects*; D007306:Insecticides / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D007301:Insect Hormones; D007306:Insecticides; D026941:Sodium Channel Blockers
keywords: ADME; anthranilic diamides; bioavailability; cyantraniliprole; dibenzoyl hydrazine; ecdysone agonist; halofenozide; indoxacarb; methoxyfenozide; oxadiazine; sodium channel blocker insecticide; tebufenozide