Disrupting Acetyl-lysine Interactions: Recent Advance in the Development of BET Inhibitors
Histone acetylation is an essential approach of post-translational modification (PTM) and a significant component of epigenetic regulation that is mediated by Bromodomainscontaining protein (BRDs). In recent years, many researchers have found that a variety of malignancy, inflammatory and other dise...
Saved in:
Published in | Current drug targets Vol. 19; no. 10; p. 1148 |
---|---|
Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United Arab Emirates
01.01.2018
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | Histone acetylation is an essential approach of post-translational modification (PTM) and a significant component of epigenetic regulation that is mediated by Bromodomainscontaining protein (BRDs). In recent years, many researchers have found that a variety of malignancy, inflammatory and other diseases occurrences and developments are associated with BRD4 expression disorders or dysfunction. Meanwhile, many inhibitors of the extra-terminal (BET) family have been reported in many papers.
This review summarized those newly found BET inhibitors, their mechanism of action and bioactivity. Secondly, those compounds were mainly classified based on their structures and their structure-activity relationship information was discussed. Beyond that, every compound's design strategy was pointed out.
Herein, the recent advances reported were reviewed for discovering more excellent small molecule inhibitors. Currently, in addition to compound 4, compounds 7, 22 and 90, have also been into the clinical trial stage. In the view of the outstanding performance of BET inhibitors in anti-tumor, anti-inflammatory and anti-drug resistance, we believe that more and more BET inhibitors will become the new epigenetic therapy for cancer, inflammation and autoimmune disease in clinical practice in the near future. |
---|---|
AbstractList | Histone acetylation is an essential approach of post-translational modification (PTM) and a significant component of epigenetic regulation that is mediated by Bromodomainscontaining protein (BRDs). In recent years, many researchers have found that a variety of malignancy, inflammatory and other diseases occurrences and developments are associated with BRD4 expression disorders or dysfunction. Meanwhile, many inhibitors of the extra-terminal (BET) family have been reported in many papers.
This review summarized those newly found BET inhibitors, their mechanism of action and bioactivity. Secondly, those compounds were mainly classified based on their structures and their structure-activity relationship information was discussed. Beyond that, every compound's design strategy was pointed out.
Herein, the recent advances reported were reviewed for discovering more excellent small molecule inhibitors. Currently, in addition to compound 4, compounds 7, 22 and 90, have also been into the clinical trial stage. In the view of the outstanding performance of BET inhibitors in anti-tumor, anti-inflammatory and anti-drug resistance, we believe that more and more BET inhibitors will become the new epigenetic therapy for cancer, inflammation and autoimmune disease in clinical practice in the near future. |
Author | Ma, Shutao Zhang, Fa |
Author_xml | – sequence: 1 givenname: Fa surname: Zhang fullname: Zhang, Fa – sequence: 2 givenname: Shutao surname: Ma fullname: Ma, Shutao organization: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, China |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29189147$$D View this record in MEDLINE/PubMed |
BookMark | eNo1j11LwzAYhYMoOqd_QeIPqO7NR5N4V7epg4Eg88abkaRvXaBNS5sN-u83Ua8OnIfzwLkm57GNSMg9zB4YKPEIXBshZwAmz3NQAMxALgVTZ2QCWvFMSsMuydWp1gaEmpCvRRj6fZdC_KaFxzTWWT0OISJdxYS99Sm0cXiiH-gxJlqUBxs90hBp2iFd4AHrtmt-UFvR5-XmNNsFF1LbDzfkorL1gLd_OSWfL8vN_C1bv7-u5sU6c0KxlFWSaVt5wYWSXjvPS1uh0F55LtAYUwKXzsmcO10yC7m2olQOkHtvXeUsm5K7X2-3dw2W264Pje3H7f9JdgSwZVSL |
CitedBy_id | crossref_primary_10_1021_acs_jmedchem_0c00075 crossref_primary_10_1021_acs_jmedchem_1c01747 crossref_primary_10_1021_acsomega_9b02693 crossref_primary_10_1039_D0RA07971E crossref_primary_10_3390_cancers13184614 crossref_primary_10_1021_acsmedchemlett_1c00294 crossref_primary_10_1021_acs_jmedchem_4c00959 crossref_primary_10_1016_j_bmcl_2019_06_028 crossref_primary_10_1016_j_jhazmat_2021_127110 crossref_primary_10_1039_C8MD00198G crossref_primary_10_1016_j_bcp_2021_114435 crossref_primary_10_1161_CIRCRESAHA_120_315929 crossref_primary_10_3390_cancers11081193 |
ContentType | Journal Article |
Copyright | Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. |
Copyright_xml | – notice: Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. |
DBID | NPM |
DOI | 10.2174/1389450119666171129165427 |
DatabaseName | PubMed |
DatabaseTitle | PubMed |
DatabaseTitleList | PubMed |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
EISSN | 1873-5592 |
ExternalDocumentID | 29189147 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GroupedDBID | NPM |
ID | FETCH-LOGICAL-b472t-f528afc43475c8bc3dafe48c7c34e999d135bb563b8d2a168a4d7b1e3ccabfba2 |
IngestDate | Sat Sep 18 02:21:30 EDT 2021 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 10 |
Keywords | BRDs SARs chromatin transcriptional regulation acetyl-lysine BET inhibitors |
Language | English |
License | Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-b472t-f528afc43475c8bc3dafe48c7c34e999d135bb563b8d2a168a4d7b1e3ccabfba2 |
PMID | 29189147 |
ParticipantIDs | pubmed_primary_29189147 |
PublicationCentury | 2000 |
PublicationDate | 2018-01-01 |
PublicationDateYYYYMMDD | 2018-01-01 |
PublicationDate_xml | – month: 01 year: 2018 text: 2018-01-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | United Arab Emirates |
PublicationPlace_xml | – name: United Arab Emirates |
PublicationTitle | Current drug targets |
PublicationTitleAlternate | Curr Drug Targets |
PublicationYear | 2018 |
Score | 2.3226411 |
Snippet | Histone acetylation is an essential approach of post-translational modification (PTM) and a significant component of epigenetic regulation that is mediated by... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 1148 |
Title | Disrupting Acetyl-lysine Interactions: Recent Advance in the Development of BET Inhibitors |
URI | https://www.ncbi.nlm.nih.gov/pubmed/29189147 |
Volume | 19 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnZ1bS8MwFMeDFxBfRPF-I4JvUl2btEl9m5chgiK4wfBFkiZxA-2Gdg_66T1pui0OB9OXUhpSSn7N6f-k55wgdExqigkFE0nFIN_A-rFAqBRcFUpNAnKDaVFGW9wnNy16247b411Ry-ySQp5mX7_mlfyHKlwDrjZL9g9kRzeFC3AOfOEIhOE4E-Or7sf7oF8GLtczXXy-BrbASF6FQ7qUhSrkzQZhntTdD_9hbKMXMGQ148V1Ezp2urJrd-DxVeuwiJN6H7ycuNjxkRQfrTg3Rgb-rhSkj51BIXr-qkLIvVUF7SwhZyQAd-OnqUz9V6LmGT7rVv1mka3HYxcHQBfR2NaXA3cpZFbk2TQqVxbAI9V_K1FBK09DOkPrRLHsYdM8mmfcGrz7h7sldFQ9yNnUx7A1oauuE_5FqTOaq2ilchBw3dFeQ3M6X0dPY9L4B2nskz7HjjOuOONujoEz9jjjnsHAGY85b6BW47p5eRNUu2IEkrKoCEwccWEySiiLMy4zooTRlGcsI1SD3FchiaWMEyK5ikSYcEEVk6EmMFelkSLaRAt5L9fbCBujUhMlmZYEZDF0YBF87UIaGyFqOg130JYbiue-K33yPByk3akte2h5_D7to0UDc00fgHAr5GGJ4xtLlkH0 |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Disrupting+Acetyl-lysine+Interactions%3A+Recent+Advance+in+the+Development+of+BET+Inhibitors&rft.jtitle=Current+drug+targets&rft.au=Zhang%2C+Fa&rft.au=Ma%2C+Shutao&rft.date=2018-01-01&rft.eissn=1873-5592&rft.volume=19&rft.issue=10&rft.spage=1148&rft_id=info:doi/10.2174%2F1389450119666171129165427&rft_id=info%3Apmid%2F29189147&rft_id=info%3Apmid%2F29189147&rft.externalDocID=29189147 |