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Scaffold hopping enables direct access to more potent PROTACs with in vivo activity.

ABSTRACT: 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.

SUBMITTER: Burslem GM

PROVIDER: S-EPMC7404552 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Scaffold hopping enables direct access to more potent PROTACs with in vivo activity.

Burslem George M GM Bondeson Daniel P DP Crews Craig M CM

Chemical communications (Cambridge, England) 20200601 50

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. ...[more]

PMID: 32519703

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