Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors

HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failu...

Full description

Saved in:
Bibliographic Details
Published in:Medicinal chemistry research 2023, Vol.32 (1), p.1-14
Main Authors: Faridoon, Zha, Yuqi Lavender, Zhang, Guiping, Li, Jie Jack
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Congestive heart failure
Cytoplasm
Deacetylation
Fibrosis
Heart diseases
Histones
Hsp90 protein
Inflammatory diseases
Inhibitors
Inorganic Chemistry
Medicinal Chemistry
Microtubules
Neurodegenerative diseases
Oxadiazoles
Pain
Pharmacology/Toxicology
Review Article
Tubulin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c319t-7e6d2e1c1381c0ae174e16d1acb5bb784e50a654d6d660582a4ba0ca4e6ebf333
cites cdi_FETCH-LOGICAL-c319t-7e6d2e1c1381c0ae174e16d1acb5bb784e50a654d6d660582a4ba0ca4e6ebf333
container_end_page 14
container_issue 1
container_start_page 1
container_title Medicinal chemistry research
container_volume 32
creator Faridoon
Zha, Yuqi Lavender
Zhang, Guiping
Li, Jie Jack
description HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-oxadiazoles, especially difluoromethyl 1,3,4-oxadiazoles, are promising HDAC6 inhibitors for the treatment of chronic diseases such as heart failure, neurodegenerative diseases, fibrosis, and pain. Graphical abstract
doi_str_mv 10.1007/s00044-022-02987-8
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2761211493</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2761211493</sourcerecordid><originalsourceid>FETCH-LOGICAL-c319t-7e6d2e1c1381c0ae174e16d1acb5bb784e50a654d6d660582a4ba0ca4e6ebf333</originalsourceid><addsrcrecordid>eNp9kE1LAzEQhoMoWKt_wNOC59XJ9_ZY6keFihc9h2x22k1pd2uSiv33pq7gzcMw7-F5B-Yh5JrCLQXQdxEAhCiBsTyTSpfVCRlRKUVZUQanOUPOTDJ-Ti5iXANwDUKOyOIFG-98ZzeFa3HrYwqHwnfRr9oUc0h90fVd2R6a0H_ZrU1YzO-nM1VE3KBL_hMz1Prapz7ES3K2tJuIV797TN4fH95m83Lx-vQ8my5Kx-kklRpVw5A6yivqwCLVAqlqqHW1rGtdCZRglRSNapQCWTEragvOClRYLznnY3Iz3N2F_mOPMZl1vw_5h2iYVpRRKiZHig2UC32MAZdmF_zWhoOhYI7WzGDNZGvmx5qpcokPpZjhboXh7_Q_rW92NnAP</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2761211493</pqid></control><display><type>article</type><title>Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors</title><source>Springer Nature</source><creator>Faridoon ; Zha, Yuqi Lavender ; Zhang, Guiping ; Li, Jie Jack</creator><creatorcontrib>Faridoon ; Zha, Yuqi Lavender ; Zhang, Guiping ; Li, Jie Jack</creatorcontrib><description>HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-oxadiazoles, especially difluoromethyl 1,3,4-oxadiazoles, are promising HDAC6 inhibitors for the treatment of chronic diseases such as heart failure, neurodegenerative diseases, fibrosis, and pain. Graphical abstract</description><identifier>ISSN: 1054-2523</identifier><identifier>EISSN: 1554-8120</identifier><identifier>DOI: 10.1007/s00044-022-02987-8</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Bioorganic Chemistry ; Congestive heart failure ; Cytoplasm ; Deacetylation ; Fibrosis ; Heart diseases ; Histones ; Hsp90 protein ; Inflammatory diseases ; Inhibitors ; Inorganic Chemistry ; Medicinal Chemistry ; Microtubules ; Neurodegenerative diseases ; Oxadiazoles ; Pain ; Pharmacology/Toxicology ; Review Article ; Tubulin</subject><ispartof>Medicinal chemistry research, 2023, Vol.32 (1), p.1-14</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c319t-7e6d2e1c1381c0ae174e16d1acb5bb784e50a654d6d660582a4ba0ca4e6ebf333</citedby><cites>FETCH-LOGICAL-c319t-7e6d2e1c1381c0ae174e16d1acb5bb784e50a654d6d660582a4ba0ca4e6ebf333</cites><orcidid>0000-0001-9818-4773 ; 0000-0003-0991-2471</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Faridoon</creatorcontrib><creatorcontrib>Zha, Yuqi Lavender</creatorcontrib><creatorcontrib>Zhang, Guiping</creatorcontrib><creatorcontrib>Li, Jie Jack</creatorcontrib><title>Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors</title><title>Medicinal chemistry research</title><addtitle>Med Chem Res</addtitle><description>HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-oxadiazoles, especially difluoromethyl 1,3,4-oxadiazoles, are promising HDAC6 inhibitors for the treatment of chronic diseases such as heart failure, neurodegenerative diseases, fibrosis, and pain. Graphical abstract</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bioorganic Chemistry</subject><subject>Congestive heart failure</subject><subject>Cytoplasm</subject><subject>Deacetylation</subject><subject>Fibrosis</subject><subject>Heart diseases</subject><subject>Histones</subject><subject>Hsp90 protein</subject><subject>Inflammatory diseases</subject><subject>Inhibitors</subject><subject>Inorganic Chemistry</subject><subject>Medicinal Chemistry</subject><subject>Microtubules</subject><subject>Neurodegenerative diseases</subject><subject>Oxadiazoles</subject><subject>Pain</subject><subject>Pharmacology/Toxicology</subject><subject>Review Article</subject><subject>Tubulin</subject><issn>1054-2523</issn><issn>1554-8120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEQhoMoWKt_wNOC59XJ9_ZY6keFihc9h2x22k1pd2uSiv33pq7gzcMw7-F5B-Yh5JrCLQXQdxEAhCiBsTyTSpfVCRlRKUVZUQanOUPOTDJ-Ti5iXANwDUKOyOIFG-98ZzeFa3HrYwqHwnfRr9oUc0h90fVd2R6a0H_ZrU1YzO-nM1VE3KBL_hMz1Prapz7ES3K2tJuIV797TN4fH95m83Lx-vQ8my5Kx-kklRpVw5A6yivqwCLVAqlqqHW1rGtdCZRglRSNapQCWTEragvOClRYLznnY3Iz3N2F_mOPMZl1vw_5h2iYVpRRKiZHig2UC32MAZdmF_zWhoOhYI7WzGDNZGvmx5qpcokPpZjhboXh7_Q_rW92NnAP</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Faridoon</creator><creator>Zha, Yuqi Lavender</creator><creator>Zhang, Guiping</creator><creator>Li, Jie Jack</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0001-9818-4773</orcidid><orcidid>https://orcid.org/0000-0003-0991-2471</orcidid></search><sort><creationdate>2023</creationdate><title>Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors</title><author>Faridoon ; Zha, Yuqi Lavender ; Zhang, Guiping ; Li, Jie Jack</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-7e6d2e1c1381c0ae174e16d1acb5bb784e50a654d6d660582a4ba0ca4e6ebf333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bioorganic Chemistry</topic><topic>Congestive heart failure</topic><topic>Cytoplasm</topic><topic>Deacetylation</topic><topic>Fibrosis</topic><topic>Heart diseases</topic><topic>Histones</topic><topic>Hsp90 protein</topic><topic>Inflammatory diseases</topic><topic>Inhibitors</topic><topic>Inorganic Chemistry</topic><topic>Medicinal Chemistry</topic><topic>Microtubules</topic><topic>Neurodegenerative diseases</topic><topic>Oxadiazoles</topic><topic>Pain</topic><topic>Pharmacology/Toxicology</topic><topic>Review Article</topic><topic>Tubulin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Faridoon</creatorcontrib><creatorcontrib>Zha, Yuqi Lavender</creatorcontrib><creatorcontrib>Zhang, Guiping</creatorcontrib><creatorcontrib>Li, Jie Jack</creatorcontrib><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Medicinal chemistry research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Faridoon</au><au>Zha, Yuqi Lavender</au><au>Zhang, Guiping</au><au>Li, Jie Jack</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors</atitle><jtitle>Medicinal chemistry research</jtitle><stitle>Med Chem Res</stitle><date>2023</date><risdate>2023</risdate><volume>32</volume><issue>1</issue><spage>1</spage><epage>14</epage><pages>1-14</pages><issn>1054-2523</issn><eissn>1554-8120</eissn><abstract>HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-oxadiazoles, especially difluoromethyl 1,3,4-oxadiazoles, are promising HDAC6 inhibitors for the treatment of chronic diseases such as heart failure, neurodegenerative diseases, fibrosis, and pain. Graphical abstract</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s00044-022-02987-8</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-9818-4773</orcidid><orcidid>https://orcid.org/0000-0003-0991-2471</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 1054-2523
ispartof Medicinal chemistry research, 2023, Vol.32 (1), p.1-14
issn 1054-2523
1554-8120
language eng
recordid cdi_proquest_journals_2761211493
source Springer Nature
subjects Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Congestive heart failure
Cytoplasm
Deacetylation
Fibrosis
Heart diseases
Histones
Hsp90 protein
Inflammatory diseases
Inhibitors
Inorganic Chemistry
Medicinal Chemistry
Microtubules
Neurodegenerative diseases
Oxadiazoles
Pain
Pharmacology/Toxicology
Review Article
Tubulin
title Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T19%3A03%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Medicinal%20chemistry%20insights%20into%20non-hydroxamate%20HDAC6%20selective%20inhibitors&rft.jtitle=Medicinal%20chemistry%20research&rft.au=Faridoon&rft.date=2023&rft.volume=32&rft.issue=1&rft.spage=1&rft.epage=14&rft.pages=1-14&rft.issn=1054-2523&rft.eissn=1554-8120&rft_id=info:doi/10.1007/s00044-022-02987-8&rft_dat=%3Cproquest_cross%3E2761211493%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c319t-7e6d2e1c1381c0ae174e16d1acb5bb784e50a654d6d660582a4ba0ca4e6ebf333%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2761211493&rft_id=info:pmid/&rfr_iscdi=true