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

Nat Commun. 2020 Sep 18;11(1):4687. doi: 10.1038/s41467-020-18377-w.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Female
  • Gene Knockout Techniques
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Knockout
  • Models, Animal
  • Peptide Hydrolases / metabolism*
  • Proteins / metabolism*
  • Proteomics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Tacrolimus Binding Protein 1A / genetics
  • Tacrolimus Binding Protein 1A / metabolism
  • Tacrolimus Binding Proteins
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*


  • Proteins
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Peptide Hydrolases
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)
  • Tacrolimus Binding Protein 1A
  • Tacrolimus Binding Proteins
  • VHL protein, human
  • VHL protein, mouse