Innovative, combinatorial and high-throughput approaches to degrader synthesis

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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