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Issue 10, 2019
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Developing degraders: principles and perspectives on design and chemical space

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Abstract

Degraders (e.g. PROTACs, SNIPERs, degronimers etc.) are a new modality offering increasing potential both as tools for basic research and therapeutic development. They occupy chemical space that lies outside the classical Lipinski ‘Rule of 5’, which poses fresh challenges for achieving cell permeability and oral bioavailability. This study presents a comprehensive database of degrader structures from the peer reviewed literature, including both optimized degraders and first generation compounds, in order to provide a thorough assessment of the chemical space associated with this modality and identify common trends used during the ‘hit to lead’ process. The results provide insights into this new area of chemical space as well as pointers for degrader design, which we anticipate will be useful for researchers entering this field.

Graphical abstract: Developing degraders: principles and perspectives on design and chemical space

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Supplementary files

Article information


Submitted
12 May 2019
Accepted
20 Jul 2019
First published
12 Aug 2019

This article is Open Access

Med. Chem. Commun., 2019,10, 1755-1764
Article type
Research Article

Developing degraders: principles and perspectives on design and chemical space

H. J. Maple, N. Clayden, A. Baron, C. Stacey and R. Felix, Med. Chem. Commun., 2019, 10, 1755
DOI: 10.1039/C9MD00272C

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