Tebufenozide (Synonyms: RH-5992)

Tebufenozide is an insecticide that acts as a non-steroidal agonist of the insect ecdysone receptor (EcR; IC₅₀ = 0.85 nM in a cell-free preparation of C. suppressalis integument).¹ It induces a premature molt and is lethal to S. litura third instar larva (LD₅₀ = 0.33 µM per larva).^1,2 It also inhibits p-glycoprotein activity in LLC-PK1 porcine kidney epithelial cells transfected with human MDR1, the gene for p-glycoprotein (IC₅₀ = 21.5 µM).³ Tebufenozide has low toxicity in mammals, birds, and most aquatic species, but it dose-dependently decreases colony formation and induces apoptosis and cell cycle arrest in HeLa cells when used at concentrations ranging from 50 to 200 µg/ml.^4,5

1.Minakuchi, C., Nakagawa, Y., Kamimura, M., et al.Binding affinity of nonsteroidal ecdysone agonists against the ecdysone receptor complex determines the strength of their molting hormonal activityEur. J. Biochem.270(20)4095-4104(2003) 2.Yokoi, T., Minami, S., Nakagawa, Y., et al.Structure-activity relationship of imidazothiadiazole analogs for the binding to the ecdysone receptor of insect cellsPestic. Biochem. Physiol.12040-50(2015) 3.Miyata, K.-i., Nakagawa, Y., Kimura, Y., et al.Structure-activity relationships of dibenzoylhydrazines for the inhibition of P-glycoprotein-mediated quinidine transportBioorg. Med. Chem.24(14)3184-3191(2016) 4.Xu, W., Wang, B., Yang, M., et al.Tebufenozide induces G1/S cell cycle arrest and apoptosis in human cellsEnviron. Toxicol. Pharmacol.4989-96(2017) 5.Abass, K.M.An investigation into the formation of tebufenozide's toxic aromatic amine metabolites in human in vitro hepatic microsomesPestic. Biochem. Physiol.13373-78(2016)