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. Author manuscript; available in PMC: 2015 Nov 2.
Published in final edited form as: Nat Chem Biol. 2015 Jun 10;11(8):611–617. doi: 10.1038/nchembio.1858

Figure 1.

Figure 1

Proteolysis targeting chimeras (PROTACs). (a) Proposed model of PROTAC-induced degradation. Von Hippel–Lindau protein (VHL, gray) is an E3 ubiquitin ligase that, under normoxic conditions, functions with a cullin RING ligase (green and yellow) to degrade HIF1α. PROTACs recruit VHL to target proteins to induce their ubiquitination and subsequent proteasome-mediated downregulation. PROTACs were generated to two target proteins: the orphan nuclear receptor ERRα and the protein kinase RIPK2. (b) Structure of PROTAC_ERRα. The parent ERRα ligand is shown in orange and the modular VHL ligand in blue, with asterisks indicating stereocenter(s) whose inversion (in PROTAC_ERRα_epi) abolishes VHL binding. (c) Structure of PROTAC_RIPK2. The parent RIPK2 ligand is shown in green and the modular VHL ligand in blue, as in b.