Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three‐step virtual screening procedure uses a three‐dimensional pharmacophore model, docking and Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) rescoring routine. A novel hit (VS14) with good binding activity against Plutella xylostella EcR was identified from a library of over 200,000 chemicals. Subsequently, the 1‐phenyl‐4‐cyano‐5‐aminopyrazole scaffold and twelve EcR ligands were synthesized. Their IC₅₀ values against Plutella xylostella EcR ranged from 0.64 to 23.21 μm. Furthermore, a preliminary analysis of the structure–activity relationship for novel scaffolds provided a basis for designing new ligands with improved activity.

中文翻译：

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通过虚拟筛选、结构优化和生物学评估鉴定 1-苯基-4-氰基-5-氨基吡唑作为新型蜕皮激素受体配体。

蜕皮激素通过与蜕皮激素受体 (EcR) 结合来启动昆虫的蜕皮过程，蜕皮激素受体是鉴定昆虫生长调节剂的一个有希望的目标。本文介绍了一种用于识别新 EcR 配体的计算机/体外筛选程序。三步虚拟筛选程序使用三维药效团模型、对接和分子力学/泊松-玻尔兹曼表面积 (MM/PBSA) 重新评分程序。一种新型的命中（VS14）具有良好的抗结合活性菜 蛾的EcR从超过20万的化学品库标识。随后，合成了 1-苯基-4-氰基-5-氨基吡唑支架和十二个 EcR 配体。他们对小菜蛾的IC ₅₀值EcR 范围从 0.64 到 23.21 μm。此外，对新型支架的构效关系的初步分析为设计具有改进活性的新配体提供了基础。