Scaffold hopping enables direct access to more potent PROTACs with in vivo activity
- Resource Type
- Authors
- Daniel P. Bondeson; Craig M. Crews; George M. Burslem
- Source
- Chem Commun (Camb)
- Subject
- Ubiquitin-Protein Ligases
Fusion Proteins, bcr-abl
Mice, Nude
Antineoplastic Agents
Scaffold hopping
01 natural sciences
Article
Catalysis
03 medical and health sciences
In vivo
Neoplasms
Materials Chemistry
Animals
Humans
030304 developmental biology
0303 health sciences
010405 organic chemistry
Chemistry
Metals and Alloys
General Chemistry
0104 chemical sciences
Surfaces, Coatings and Films
Electronic, Optical and Magnetic Materials
Cell biology
Proteolysis
Ceramics and Composites
K562 Cells
Linker
- Language
- ISSN
- 1364-548X
1359-7345
Herein we employ a scaffold hopping approach to enhance the activity of a previously reported BCR-Abl PROTAC. This represents a significant advance in the PROTAC field since it can abrogate the need to optimize the linker to access a more potent degrader. The new PROTAC demonstrates a >10 fold increase in ability to induce degradation and demonstrates in vivo activity.