(S,R,S)-VL285 Phenol-piperazine-pyridine-alkyne-NH₂ hydrochloride

Protein degrader building block (S,R,S)-VL285 Phenol-piperazine-pyridine-alkyne-NH₂ hydrochloride enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a von Hippel-Lindau (VHL)-recruiting ligand with alternative exit vector from the widely used VH032 (901490), a rigid inker, and a pendant amine for reactivity with a carboxylic acid on the target ligand. Because even slight alterations in ligands and crosslinkers can affect ternary complex formation between the target, E3 ligase, and PROTAC, many analogs are prepared to screen for optimal target degradation. When used with other protein degrader building blocks with a terminal amine, parallel synthesis can be used to more quickly generate PROTAC libraries that feature variation in crosslinker length, composition, and E3 ligase ligand.

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PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license