Discovery of BET bromodomain inhibitors and their role in target validation

Bromodomains (BRDs) are protein interaction modules that selectively recognize ε-N-acetylated lysine residues. BRDs are present in diverse proteins that play key functions in chromatin organization and regulation of gene transcription. Aberrant transcription is a hallmark of many diseases in particu...

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Main Authors: Mueller, S, Knapp, S
Format: Journal article
Language:English
Published: Royal Society of Chemistry 2014
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author Mueller, S
Knapp, S
author_facet Mueller, S
Knapp, S
author_sort Mueller, S
collection OXFORD
description Bromodomains (BRDs) are protein interaction modules that selectively recognize ε-N-acetylated lysine residues. BRDs are present in diverse proteins that play key functions in chromatin organization and regulation of gene transcription. Aberrant transcription is a hallmark of many diseases in particular cancer and inflammation. The complexity of molecular processes regulating gene transcription identified transcriptional regulators as interesting targets for the development of specific chemical tool molecules (chemical probes) that help to understand the molecular mechanisms of transcription and to explore the potential of BRD mediated interactions as sites for pharmaceutical intervention. Recently a number of highly specific inhibitors have been developed against the BET (bromo and extra terminal) family of bromodomains. The availability of selective BRD inhibitors had a significant impact on the validation of bromodomain-containing proteins as targets for drug development and for our understanding of the biological roles of these proteins. In this review we will summarize the discovery of BET bromodomain inhibitors and their roles in target validation. © 2014 The Royal Society of Chemistry.
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spelling oxford-uuid:bcaaa80b-6928-44b8-85b0-9a598f8e795e2022-03-27T05:25:59ZDiscovery of BET bromodomain inhibitors and their role in target validationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bcaaa80b-6928-44b8-85b0-9a598f8e795eEnglishSymplectic Elements at OxfordRoyal Society of Chemistry2014Mueller, SKnapp, SBromodomains (BRDs) are protein interaction modules that selectively recognize ε-N-acetylated lysine residues. BRDs are present in diverse proteins that play key functions in chromatin organization and regulation of gene transcription. Aberrant transcription is a hallmark of many diseases in particular cancer and inflammation. The complexity of molecular processes regulating gene transcription identified transcriptional regulators as interesting targets for the development of specific chemical tool molecules (chemical probes) that help to understand the molecular mechanisms of transcription and to explore the potential of BRD mediated interactions as sites for pharmaceutical intervention. Recently a number of highly specific inhibitors have been developed against the BET (bromo and extra terminal) family of bromodomains. The availability of selective BRD inhibitors had a significant impact on the validation of bromodomain-containing proteins as targets for drug development and for our understanding of the biological roles of these proteins. In this review we will summarize the discovery of BET bromodomain inhibitors and their roles in target validation. © 2014 The Royal Society of Chemistry.
spellingShingle Mueller, S
Knapp, S
Discovery of BET bromodomain inhibitors and their role in target validation
title Discovery of BET bromodomain inhibitors and their role in target validation
title_full Discovery of BET bromodomain inhibitors and their role in target validation
title_fullStr Discovery of BET bromodomain inhibitors and their role in target validation
title_full_unstemmed Discovery of BET bromodomain inhibitors and their role in target validation
title_short Discovery of BET bromodomain inhibitors and their role in target validation
title_sort discovery of bet bromodomain inhibitors and their role in target validation
work_keys_str_mv AT muellers discoveryofbetbromodomaininhibitorsandtheirroleintargetvalidation
AT knapps discoveryofbetbromodomaininhibitorsandtheirroleintargetvalidation