Figure 2.

This diagram shows the mode of action of folate–pomalidomide and folate-conjugated pomalidomide-based PROTACs. Upon binding FOLR1 on the cell membrane (1), folate-pomalidomide or folate-conjugated IMiD-based PROTACs are transported into cells, and the active pomalidomide or PROTACs are released after the reduction by endogenous GSH (2). The active pomalidomide or PROTACs recruit endogenous CRBN E3 ligase (similar to the model shown in Figure 1B), leading to polyubiquitination and subsequent degradation of the glued proteins of interest (POIs, neosubstrates) by the UPS (3). This figure is adapted from an original paper by Chen et al. [14].