title: Potent and selective partial ecdysone agonist activity of chromafenozide in Sf9 cells.
abstract: Chromafenozide (ANS-118) is a non-steroidal ecdysone mimic and its insecticidal effect is highly specific to lepidoptera. In order to evaluate the transcription-inducing activity via nuclear ecdysone receptor (EcR) and the mode of action of chromafenozide, ecdysone-responsive reporter gene assay systems were developed in Sf9 and Kc cells. Ponasterone A, a full EcR agonist, induced reporter transcription in a dose-dependent manner in both Sf9 and Kc cells. In contrast, chromafenozide activated reporter transcription with comparable potency to ponasterone A only in Sf9 cells, although its maximum activity was 4-fold lower than that of ponasterone A. When chromafenozide was applied together with ponasterone A to Sf9 cells, it antagonized ponasterone A at nanomolar concentrations. These results suggest that chromafenozide is a potent partial EcR agonist specific to lepidoptera; it appears to bind lepidopteran EcR with comparable affinity to ponasterone A, but may activate the EcR in a different manner.
authors.affiliation: Research & Development Laboratories, Nippon Kayaku Company, Ltd., 225-1 Koshikiya, Saitama, Ageo, 362-0064, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukasawa
authors.forename: Akio
authors.initials: A
authors.lastname: Masui
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004440:Ecdysone / Q000819:agonists*; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects / Q000502:physiology; D006834:Hydrazines / Q000494:pharmacology*; D007306:Insecticides; D007915:Lepidoptera; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000819:agonists; D013045:Species Specificity; D018411:Spodoptera / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001578:Benzopyrans; D006834:Hydrazines; D007306:Insecticides; D011987:Receptors, Steroid; C055469:ecdysone receptor; C454111:chromafenozide; D004440:Ecdysone; D004441:Ecdysterone; C008999:ponasterone A; D008156:Luciferases