Abstract:
As a cutting-edge approach in biomedicine, proteolysis-targeting chimeras (PROTACs) technology eliminates target proteins through an event driven degradation mode. Its high selectivity and unique mechanism have made it a research hotspot in medicine, agrochemistry, and other fields. In this study, PROTACs were leveraged to conjugate chlorantraniliprole and pomalidomide via alkyl chains or polyethylene glycol chains to constructeight novel PROTACs molecules targeting the ryanodine receptor (RyR). Biological activity assays showed that the target compounds exhibited good insecticidal activity against the Lepidopteran pests
Plutella xylostella and
Mythimna separata, with the lethality both exceeding 80% at the concentration of 50 mg/L. Among them, LC
50 values of 0.50 μmol/L for compound
A8 against
Plutella xylostella and 1.13 μmol/L for
A5 against
Mythimna separata, representing 5.6-fold and 28-fold reductions in potency compared to chlorantraniliprole, respectively. Western blot analysis indicated that none of the compounds induced RyR degradation, potentially due to insufficient ligand binding affinity or inefficient ubiquitin transfer. Subsequent optimization should focus on E3 ligase ligands and linker structures. This work lays a foundation for applying PROTACs technology to pesticide development.