A new binding mode for ecdysteroid analog tebufenozide as a multitargeted IGR with chitinase

Tebufenozide, an efficient insect growth regulator (IGR) against lepidopteran pests, presents a novel mode of action with minimal non-target impact. By competing with ecdysteroids for ecdysone receptor (EcR) binding, it regulates insect growth precisely. This study explores tebufenozide's potential as a multitarget IGR, targeting both EcR and Ostrinia furnacalis chitinase I (OfChtI). The inhibitory activity against OfChtI is comparable to that of substrates (GlcNAc)5, with an IC50 of 45.77 ​μM. Our computational findings indicate that tebufenozide binds at the subsite −1 to +1 of OfChtI through various interactions. Notably, tebufenozide establishes a pi-pi interaction with the flipped sidechain of Trp107, enabling tebufenozide to deeply penetrate into the S1 pocket, thereby obstructing substrate binding to OfChtI. These insights highlight the potency of multitarget strategies, laying the groundwork for innovative IGR designs that offer comprehensive pest management solutions.