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. 2019 Sep 8;24(18):3272. doi: 10.3390/molecules24183272

Figure 1.

Figure 1

The schematic representation of the different ubiquitin dependent degraders. (A) Protein-targeting chimeric molecules (PROTACs) and specific and non-genetic IAP-dependent protein erasers (SNIPERs) bind to the target protein and recruit their respective E3 ligase which, in turn, is then bound by a cognate E2 ligase resulting in the ubiquitination (Ub, ubiquitin) of the target protein and 26S proteasomal (P) degradation. cIAP1 can undergo autoubiquitination and be degraded simultaneously with the target protein. (B) In-cell click-formed proteolysis targeting chimeras (CLIPTACs) comprise two separate ligands that undergo cycloaddition (click) in the cell forming a bifunctional degrader, subsequently allowing for target protein degradation. PD, phthalimide derivative (lenalidomide, thalidomide, pomalidomide or TD-106), CRL4, cullin-ring E3 ligase 4 complex; VHL, Von Hippel–Lindau E3 ligase complex; cIAP1, anti-apoptotic protein 1; ME-BS, bestatin derivative.