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Issue 12, 2016
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Small molecule-mediated protein knockdown as a new approach to drug discovery

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Abstract

The concept of using peptidic bifunctional molecules to allow recruitment of ubiquitin E3 ligases to induce the degradation of specific intracellular proteins was first demonstrated in 2001 but, following the extension of this approach to non-peptidic agents, its utility has been greatly expanded. As the number of E3 ligases amenable to recruitment also continues to grow, induced protein degradation now represents a new pharmacological strategy for highly efficient chemical protein knockdown with utility both as a chemical biology tool and also potentially as a clinically-useful therapeutic modality. We survey some of the recent advances in the design of small molecule chemical inducers of protein degradation and the potential challenges that will need to be overcome in order to allow clinical evaluation.

Graphical abstract: Small molecule-mediated protein knockdown as a new approach to drug discovery

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Publication details

The article was received on 23 Jun 2016, accepted on 24 Jul 2016 and first published on 26 Jul 2016


Article type: Review Article
DOI: 10.1039/C6MD00347H
Citation: Med. Chem. Commun., 2016,7, 2206-2216
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    Small molecule-mediated protein knockdown as a new approach to drug discovery

    C. P. Tinworth, H. Lithgow and I. Churcher, Med. Chem. Commun., 2016, 7, 2206
    DOI: 10.1039/C6MD00347H

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