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

Author

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, and William Farnaby

Subjects
Science
Abstract

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.

Published
2022
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