Mar 16, 2020

Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

Behnam NabetNathanael S Gray


Chemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic approaches and improved selectivity over small molecule inhibitors. We describe dTAGV-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12F36V-tagged proteins. dTAGV-1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, supports combination degrader studies and facilitates investigations of protein function in cells and mice.

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Mentioned in this Paper

Enzyme Inhibitor Drugs
CRBN protein, human
Mulberrofuran G
Laboratory mice
Protein Function
VHL protein, human

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