A new nonsteroidal chemical class of ligand for the ecdysteroid receptor 3, 5-di-tert-butyl-4-hydroxy-N-isobutyl-benzamide shows apparent insect molting hormone activities at molecular and cellular levels.
Insect molting hormones, ecdysteroids, found in natural products so far have steroidal structures. However, nonsteroidal ecdysteroid agonists show promise as a new type of insecticide and may be useful as probes for the biochemical study of ecdysteroids. 3, 5-Di-tert-butyl-4-hydroxy-N-isobutyl-benzamide (DTBHIB), discovered by the combination of the automated ecdysteroid receptor binding assay and the ecdysteroid responsive gene expression assay, showed both ecdysteroid receptor binding activity and induction activities of ecdysteroid responsive genes. Furthermore, the inhibition of the Kc cell proliferation and the induction of the cell process protrusion were observed in the presence of DTBHIB in a dose response manner. A similar compound of DTBHIB, however, could neither bind the receptor nor induce the responsive gene. These results provide strong evidence for the ecdysteroid agonist activity of DTBHIB, which has a novel nonsteroidal chemical structure, and might be a valuable lead chemical for higher potential ecdysteroid agonists.
Mikitani
K
K
Agricultural Chemicals Research Laboratory, Sumitomo Chemical Co., Ltd., Hyogo, Japan.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004331:Drosophila melanogaster; D004441:Ecdysterone / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression; D007301:Insect Hormones / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008156:Luciferases / Q000096:biosynthesis; D011869:Radioligand Assay; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
C101984:3,5-di-tert-butyl-4-hydroxy-N-isobutylbenzamide; D001549:Benzamides; D007301:Insect Hormones; D008024:Ligands; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; C034808:ecdysteroid receptor; D004441:Ecdysterone; C008999:ponasterone A; D008156:Luciferases