Optimisation of protein degraders requires balancing multiple factors including potency, cell permeability and solubility. Here we show that the fluorescence of pomalidomide can be used in high-throughput screening assays to rapidly assess cellular penetration of degrader candidates. In addition, this technique can be paired with endocytosis inhibitors to gain insight into potential mechanisms of candidates entering a target cell. A model library of pomalidomide conjugates was synthesised and evaluated using high-throughput fluorescence microscopy. This technique based on intrinsic fluorescence can be used to guide rational design of pomalidomide conjugates without the need for additional labels or tags.

中文翻译：

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利用泊马度胺的固有荧光进行成像应用

蛋白质降解剂的优化需要平衡多种因素，包括效力、细胞渗透性和溶解度。在这里，我们证明泊马度胺的荧光可用于高通量筛选测定，以快速评估候选降解剂的细胞渗透性。此外，该技术可以与内吞作用抑制剂配合使用，以深入了解候选物进入靶细胞的潜在机制。使用高通量荧光显微镜合成并评估泊马度胺缀合物模型库。这种基于内在荧光的技术可用于指导泊马度胺缀合物的合理设计，而无需额外的标记或标签。