Innovative, combinatorial and high-throughput approaches to degrader synthesis

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Stevens, Rebecca and Thompson, James D. F. and Fournier, Julie C. L. and Burley, Glenn A. and Battersby, David J. and Miah, Afjal H. (2024) Innovative, combinatorial and high-throughput approaches to degrader synthesis. Chemical Society Reviews, 53 (10). pp. 4838-4861. ISSN 0306-0012 (https://doi.org/10.1039/d3cs01127e)

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Abstract

Targeted protein degraders such as PROTACs and molecular glues are a rapidly emerging therapeutic modality within industry and academia. Degraders possess unique mechanisms of action that lead to the removal of specific proteins by co-opting the cell's natural degradation mechanisms via induced proximity. Their optimisation thus far has often been largely empirical, requiring the synthesis and screening of a large number of analogues. In addition, the synthesis and development of degraders is often challenging, leading to lengthy optimisation campaigns to deliver candidate-quality compounds. This review highlights how the synthesis of degraders has evolved in recent years, in particular focusing on means of applying high-throughput chemistry and screening approaches to expedite these timelines, which we anticipate to be valuable in shaping the future of degrader optimisation campaigns.

  • Item type:Article
    ID code:89024
    Dates:
    Date
    Event
    10 April 2024
    Published
    10 April 2024
    Published Online
    1 April 2024
    Accepted
    20 December 2023
    Submitted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:29 Apr 2024 12:39
    Last modified:11 Nov 2024 14:17
    URI:https://strathprints.strath.ac.uk/id/eprint/89024
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