Institute of Food Science, Italian National Research Council (ISA-CNR), via Roma 64, 83100 Avellino, Italy.
Molecules. 2021 Jan 18;26(2):492. doi: 10.3390/molecules26020492.
A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PIK/AKT pathway.
经过基于 AKT1 与已知抑制剂 IQO 复合物实验结构生成药效团模型，对适合结合 AKT 蛋白的天然化合物进行了计算筛选。从筛选中得到的最适合的化合物通过分子对接、ADMET（吸收、分布、代谢、排泄和毒性）分析和毒性特征进一步研究。在计算分析结束时选择了两种化合物，即 ZINC2429155（也称为 STL1）和 ZINC1447881（也称为 AC1），与 IQO 作为阳性对照和槲皮素作为阴性对照一起在实验测定中进行了测试。只有 STL1 能明显抑制 AKT 的激活，从而负调控 PIK/AKT 通路。
