Advancements in the development of non-BET bromodomain chemical probes

Michael A. Clegg; Nicholas C. O. Tomkinson; Rab K. Prinjhal; Philip G. Humphreys

doi:10.1002/cmdc.201800738

Advancements in the development of non-BET bromodomain chemical probes

Michael A. Clegg, Nicholas C. O. Tomkinson, Rab K. Prinjhal, Philip G. Humphreys

Pure And Applied Chemistry

Research output: Contribution to journal › Review article › peer-review

38 Citations (Scopus)

210 Downloads (Pure)

Abstract

The bromodomain and extra terminal (BET) family of bromodomain‐containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high‐quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non‐BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non‐BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non‐BET bromodomains as tractable therapeutic targets.

Original language	English
Pages (from-to)	362-385
Number of pages	24
Journal	ChemMedChem
Volume	14
Issue number	4
Early online date	9 Jan 2019
DOIs	https://doi.org/10.1002/cmdc.201800738
Publication status	Published - 19 Feb 2019

Keywords

acetylated lysines
chemical probes
epigenetics
non-BET bromodomains
target validation

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title = "Advancements in the development of non-BET bromodomain chemical probes",

abstract = "The bromodomain and extra terminal (BET) family of bromodomain‐containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high‐quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non‐BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non‐BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non‐BET bromodomains as tractable therapeutic targets.",

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N1 - This is the peer reviewed version of the following article: Clegg, MA, Tomkinson, NCO, Prinjhal, RK & Humphreys, PG 2019, 'Advancements in the development of non-BET bromodomain chemical probes' ChemMedChem, vol. 14, no. 4, pp. 362-385, which has been published in final form at https://doi.org/10.1002/cmdc.201800738. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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N2 - The bromodomain and extra terminal (BET) family of bromodomain‐containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high‐quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non‐BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non‐BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non‐BET bromodomains as tractable therapeutic targets.

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Advancements in the development of non-BET bromodomain chemical probes

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Keywords

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