Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review
[Display omitted] Retinoic acid receptors (RARs) α, β, and γ are members of the nuclear receptor superfamily. Compounds which bind to and activate the RARs are termed retinoids which regulate a wide variety of biological processes such as vertebrate embryonic morphogenesis and organogenesis, cell gr...
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Veröffentlicht in: | Bioorganic & medicinal chemistry 2020-10, Vol.28 (20), p.115664, Article 115664 |
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Retinoic acid receptors (RARs) α, β, and γ are members of the nuclear receptor superfamily. Compounds which bind to and activate the RARs are termed retinoids which regulate a wide variety of biological processes such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation, and apoptosis, as well as their disorders. Although many synthetic selective RARα, RARβ, and RARγ agonists have been designed and prepared, these have generally been lipophilic acids without good drug-like properties and with low oral bioavailability. Recently this has been changing and drug design approaches to highly potent and selective RARα and RARβ agonists with low lipophilicity that are orally bioavailable and less toxic have been developed, that have a range of potential therapeutic uses. This review covers these new advances. |
doi_str_mv | 10.1016/j.bmc.2020.115664 |
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Retinoic acid receptors (RARs) α, β, and γ are members of the nuclear receptor superfamily. Compounds which bind to and activate the RARs are termed retinoids which regulate a wide variety of biological processes such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation, and apoptosis, as well as their disorders. Although many synthetic selective RARα, RARβ, and RARγ agonists have been designed and prepared, these have generally been lipophilic acids without good drug-like properties and with low oral bioavailability. Recently this has been changing and drug design approaches to highly potent and selective RARα and RARβ agonists with low lipophilicity that are orally bioavailable and less toxic have been developed, that have a range of potential therapeutic uses. This review covers these new advances.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2020.115664</identifier><identifier>PMID: 33069074</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>AC-261066 ; Alpha agonist ; Beta agonist ; C286 ; Nerve injury ; RAR586 ; Retinoic acid receptor ; Review ; SAR</subject><ispartof>Bioorganic & medicinal chemistry, 2020-10, Vol.28 (20), p.115664, Article 115664</ispartof><rights>2020 The Author(s)</rights><rights>Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><rights>2020 The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-ca45982a9b4ad0a37814d8b9431371d6aa874c2d89ec7941e6d7a5a7bdf5c6533</citedby><cites>FETCH-LOGICAL-c451t-ca45982a9b4ad0a37814d8b9431371d6aa874c2d89ec7941e6d7a5a7bdf5c6533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2020.115664$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33069074$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Borthwick, Alan D.</creatorcontrib><creatorcontrib>Goncalves, Maria B.</creatorcontrib><creatorcontrib>Corcoran, Jonathan P.T.</creatorcontrib><title>Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>[Display omitted]
Retinoic acid receptors (RARs) α, β, and γ are members of the nuclear receptor superfamily. Compounds which bind to and activate the RARs are termed retinoids which regulate a wide variety of biological processes such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation, and apoptosis, as well as their disorders. Although many synthetic selective RARα, RARβ, and RARγ agonists have been designed and prepared, these have generally been lipophilic acids without good drug-like properties and with low oral bioavailability. Recently this has been changing and drug design approaches to highly potent and selective RARα and RARβ agonists with low lipophilicity that are orally bioavailable and less toxic have been developed, that have a range of potential therapeutic uses. This review covers these new advances.</description><subject>AC-261066</subject><subject>Alpha agonist</subject><subject>Beta agonist</subject><subject>C286</subject><subject>Nerve injury</subject><subject>RAR586</subject><subject>Retinoic acid receptor</subject><subject>Review</subject><subject>SAR</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kF9KAzEQxoMoWqsH8EVyga3JJptNEIRS_AeCUPQ5zCZpm7LdlWRb8Vh6EM9kymrRF59mhpnvm5kfQmeUjCih4mI5qlZmlJM81bQQgu-hAeWCZ4wpuo8GRAmZEanEETqOcUkIybmih-iIMSIUKfkAVVNnXNNhsBtojIvYN7hbOGxd9PMGtzM8HU_x5zuGxvbpB4Z52_jYRQwRtwHq-g1XvoUN-BqqOmnDeh5HeIyD23j3eoIOZlBHd_odh-j55vppcpc9PN7eT8YPmeEF7TIDvFAyB1VxsARYKSm3slKcUVZSKwBkyU1upXKmVJw6YUsooKzsrDCiYGyIrnrfl3W1cnb7VjpOvwS_gvCmW_D6b6fxCz1vN7ospCzSniGivYEJbYzBzXZaSvQWuF7qBFxvgeseeNKc_166U_wQTgOX_YBLryccQUfjXUJtfXCm07b1_9h_AeMbksQ</recordid><startdate>20201015</startdate><enddate>20201015</enddate><creator>Borthwick, Alan D.</creator><creator>Goncalves, Maria B.</creator><creator>Corcoran, Jonathan P.T.</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20201015</creationdate><title>Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review</title><author>Borthwick, Alan D. ; Goncalves, Maria B. ; Corcoran, Jonathan P.T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-ca45982a9b4ad0a37814d8b9431371d6aa874c2d89ec7941e6d7a5a7bdf5c6533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>AC-261066</topic><topic>Alpha agonist</topic><topic>Beta agonist</topic><topic>C286</topic><topic>Nerve injury</topic><topic>RAR586</topic><topic>Retinoic acid receptor</topic><topic>Review</topic><topic>SAR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Borthwick, Alan D.</creatorcontrib><creatorcontrib>Goncalves, Maria B.</creatorcontrib><creatorcontrib>Corcoran, Jonathan P.T.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Borthwick, Alan D.</au><au>Goncalves, Maria B.</au><au>Corcoran, Jonathan P.T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2020-10-15</date><risdate>2020</risdate><volume>28</volume><issue>20</issue><spage>115664</spage><pages>115664-</pages><artnum>115664</artnum><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>[Display omitted]
Retinoic acid receptors (RARs) α, β, and γ are members of the nuclear receptor superfamily. Compounds which bind to and activate the RARs are termed retinoids which regulate a wide variety of biological processes such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation, and apoptosis, as well as their disorders. Although many synthetic selective RARα, RARβ, and RARγ agonists have been designed and prepared, these have generally been lipophilic acids without good drug-like properties and with low oral bioavailability. Recently this has been changing and drug design approaches to highly potent and selective RARα and RARβ agonists with low lipophilicity that are orally bioavailable and less toxic have been developed, that have a range of potential therapeutic uses. This review covers these new advances.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33069074</pmid><doi>10.1016/j.bmc.2020.115664</doi><oa>free_for_read</oa></addata></record> |
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subjects | AC-261066 Alpha agonist Beta agonist C286 Nerve injury RAR586 Retinoic acid receptor Review SAR |
title | Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review |
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