Nature Communications (Oct 2022)

A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo

  • Christiane Kofink,
  • Nicole Trainor,
  • Barbara Mair,
  • Simon Wöhrle,
  • Melanie Wurm,
  • Nikolai Mischerikow,
  • Michael J. Roy,
  • Gerd Bader,
  • Peter Greb,
  • Géraldine Garavel,
  • Emelyne Diers,
  • Ross McLennan,
  • Claire Whitworth,
  • Vesna Vetma,
  • Klaus Rumpel,
  • Maximilian Scharnweber,
  • Julian E. Fuchs,
  • Thomas Gerstberger,
  • Yunhai Cui,
  • Gabriela Gremel,
  • Paolo Chetta,
  • Stefan Hopf,
  • Nicole Budano,
  • Joerg Rinnenthal,
  • Gerhard Gmaschitz,
  • Moriz Mayer,
  • Manfred Koegl,
  • Alessio Ciulli,
  • Harald Weinstabl,
  • William Farnaby

DOI
https://doi.org/10.1038/s41467-022-33430-6
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 15

Abstract

Read online

Protein degraders are an emerging drug modality; however, their properties lie beyond typical drug-like space. Here the authors report optimisation via structure-based exit vector and linker design towards the VHL-recruiting PROTAC ACBI2, an orally bioavailable and selective degrader of SMARCA2.