含泊马度胺的联苯醚类似物作为程序性细胞死亡蛋白 1/程序性细胞死亡配体 1 相互作用的小分子抑制剂。
Biphenyl Ether Analogs Containing Pomalidomide as Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction.
机构信息
Department of Drug Design, University of Groningen, 9713 AV Groningen, The Netherlands.
Faculty of Chemistry, Jagiellonian University, 30-387 Krakow, Poland.
出版信息
Molecules. 2022 May 27;27(11):3454. doi: 10.3390/molecules27113454.
New biphenyl-based chimeric compounds containing pomalidomide were developed and evaluated for their activity to inhibit and degrade the programmed cell death-1/programmed cell death- ligand 1 (PD-1/PD-L1) complex. Most of the compounds displayed excellent inhibitory activity against PD-1/PD-L1, as assessed by the homogenous time-resolved fluorescence (HTRF) binding assay. Among them, compound is one of the best with an IC value of 60 nM. Using an ex vivo PD-1/PD-L1 blockade cell line bioassay that expresses human PD-1 and PD-L1, we show that compounds and significantly restore the repressed immunity in this co-culture model. Western blot data, however, demonstrated that these anti-PD-L1/pomalidomide chimeras could not reduce the protein levels of PD-L1.
新的联苯类嵌合体化合物含有泊马度胺，被开发并评估其抑制和降解程序性细胞死亡-1/程序性细胞死亡配体 1（PD-1/PD-L1）复合物的活性。大多数化合物通过均相时间分辨荧光（HTRF）结合测定显示出对 PD-1/PD-L1 的优异抑制活性。其中，化合物 是最好的之一，IC 值为 60 nM。使用表达人 PD-1 和 PD-L1 的体外 PD-1/PD-L1 阻断细胞系生物测定，我们表明化合物 和 显著恢复了共培养模型中受抑制的免疫。然而，Western blot 数据表明，这些抗 PD-L1/泊马度胺嵌合体不能降低 PD-L1 的蛋白水平。
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