Targeting the Estrogen Receptor for the Treatment of Breast Cancer: Recent Advances and Challenges
Estrogen receptor alpha (ERα) is a well-established therapeutic target for the treatment of ER-positive (ER+) breast cancers. Despite the tremendous successes achieved with tamoxifen, a selective ER modulator, and aromatase inhibitors (AIs), resistance to these therapies is a major clinical problem....
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2023-07, Vol.66 (13), p.8339-8381 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 8381 |
|---|---|
| container_issue | 13 |
| container_start_page | 8339 |
| container_title | Journal of medicinal chemistry |
| container_volume | 66 |
| creator | Rej, Rohan Kalyan Acharyya, Ranjan Kumar Rae, James Michael Wang, Shaomeng |
| description | Estrogen receptor alpha (ERα) is a well-established therapeutic target for the treatment of ER-positive (ER+) breast cancers. Despite the tremendous successes achieved with tamoxifen, a selective ER modulator, and aromatase inhibitors (AIs), resistance to these therapies is a major clinical problem. Therefore, induced protein degradation and covalent inhibition have been pursued as new therapeutic approaches to target ERα. This Perspective summarizes recent progress in the discovery and development of oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), and proteolysis targeting chimera (PROTAC) ER degraders. We focus on those compounds which have been advanced into clinical development. |
| doi_str_mv | 10.1021/acs.jmedchem.3c00136 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2830671932</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2830671932</sourcerecordid><originalsourceid>FETCH-LOGICAL-a394t-fc546f17b21f8f40845d94338cc1c0b1ccfc71f3c22f0c7bdb36d9f37f5c62223</originalsourceid><addsrcrecordid>eNp9kMtKAzEUhoMoWqtvIJKlm6knOenM1J0WbyAIUtdD5sxJW5lLTVLBt3d60aWLEJL_-0_IJ8SFgpECra4thdFHwxUtuBkhAShMD8RAjTUkJgdzKAYAWic61XgiTkP4AABUGo_FCWaYZWj0QJQz6-ccl-1cxgXL-xB9N-dWvjHxKnZeun5tkplnGxtuo-ycvOsPIcqpbYn9zRbug9vqa3MRpG0rOV3YuuZ2zuFMHDlbBz7f70Px_nA_mz4lL6-Pz9Pbl8TixMTE0dikTmWlVi53BnIzriYGMSdSBKUicpQph6S1A8rKqsS0mjjM3JhSrTUOxdVu7sp3n2sOsWiWgbiubcvdOhQ6R0gzNcENanYo-S4Ez65Y-WVj_XehoNjYLXq7xa_dYm-3r13uX1iXffZX-tXZA7ADtvVu7dv-w__P_AGf64ms</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2830671932</pqid></control><display><type>article</type><title>Targeting the Estrogen Receptor for the Treatment of Breast Cancer: Recent Advances and Challenges</title><source>ACS Publications</source><source>MEDLINE</source><creator>Rej, Rohan Kalyan ; Acharyya, Ranjan Kumar ; Rae, James Michael ; Wang, Shaomeng</creator><creatorcontrib>Rej, Rohan Kalyan ; Acharyya, Ranjan Kumar ; Rae, James Michael ; Wang, Shaomeng</creatorcontrib><description>Estrogen receptor alpha (ERα) is a well-established therapeutic target for the treatment of ER-positive (ER+) breast cancers. Despite the tremendous successes achieved with tamoxifen, a selective ER modulator, and aromatase inhibitors (AIs), resistance to these therapies is a major clinical problem. Therefore, induced protein degradation and covalent inhibition have been pursued as new therapeutic approaches to target ERα. This Perspective summarizes recent progress in the discovery and development of oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), and proteolysis targeting chimera (PROTAC) ER degraders. We focus on those compounds which have been advanced into clinical development.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/acs.jmedchem.3c00136</identifier><identifier>PMID: 37377342</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Aromatase Inhibitors - pharmacology ; Aromatase Inhibitors - therapeutic use ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Estrogen Antagonists - therapeutic use ; Estrogen Receptor alpha - metabolism ; Female ; Humans ; Receptors, Estrogen - metabolism ; Selective Estrogen Receptor Modulators - pharmacology ; Selective Estrogen Receptor Modulators - therapeutic use ; Tamoxifen - pharmacology ; Tamoxifen - therapeutic use</subject><ispartof>Journal of medicinal chemistry, 2023-07, Vol.66 (13), p.8339-8381</ispartof><rights>2023 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a394t-fc546f17b21f8f40845d94338cc1c0b1ccfc71f3c22f0c7bdb36d9f37f5c62223</citedby><cites>FETCH-LOGICAL-a394t-fc546f17b21f8f40845d94338cc1c0b1ccfc71f3c22f0c7bdb36d9f37f5c62223</cites><orcidid>0000-0002-8782-6950 ; 0000-0003-2239-5149</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.3c00136$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00136$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37377342$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rej, Rohan Kalyan</creatorcontrib><creatorcontrib>Acharyya, Ranjan Kumar</creatorcontrib><creatorcontrib>Rae, James Michael</creatorcontrib><creatorcontrib>Wang, Shaomeng</creatorcontrib><title>Targeting the Estrogen Receptor for the Treatment of Breast Cancer: Recent Advances and Challenges</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Estrogen receptor alpha (ERα) is a well-established therapeutic target for the treatment of ER-positive (ER+) breast cancers. Despite the tremendous successes achieved with tamoxifen, a selective ER modulator, and aromatase inhibitors (AIs), resistance to these therapies is a major clinical problem. Therefore, induced protein degradation and covalent inhibition have been pursued as new therapeutic approaches to target ERα. This Perspective summarizes recent progress in the discovery and development of oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), and proteolysis targeting chimera (PROTAC) ER degraders. We focus on those compounds which have been advanced into clinical development.</description><subject>Aromatase Inhibitors - pharmacology</subject><subject>Aromatase Inhibitors - therapeutic use</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Estrogen Antagonists - therapeutic use</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Selective Estrogen Receptor Modulators - pharmacology</subject><subject>Selective Estrogen Receptor Modulators - therapeutic use</subject><subject>Tamoxifen - pharmacology</subject><subject>Tamoxifen - therapeutic use</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKAzEUhoMoWqtvIJKlm6knOenM1J0WbyAIUtdD5sxJW5lLTVLBt3d60aWLEJL_-0_IJ8SFgpECra4thdFHwxUtuBkhAShMD8RAjTUkJgdzKAYAWic61XgiTkP4AABUGo_FCWaYZWj0QJQz6-ccl-1cxgXL-xB9N-dWvjHxKnZeun5tkplnGxtuo-ycvOsPIcqpbYn9zRbug9vqa3MRpG0rOV3YuuZ2zuFMHDlbBz7f70Px_nA_mz4lL6-Pz9Pbl8TixMTE0dikTmWlVi53BnIzriYGMSdSBKUicpQph6S1A8rKqsS0mjjM3JhSrTUOxdVu7sp3n2sOsWiWgbiubcvdOhQ6R0gzNcENanYo-S4Ez65Y-WVj_XehoNjYLXq7xa_dYm-3r13uX1iXffZX-tXZA7ADtvVu7dv-w__P_AGf64ms</recordid><startdate>20230713</startdate><enddate>20230713</enddate><creator>Rej, Rohan Kalyan</creator><creator>Acharyya, Ranjan Kumar</creator><creator>Rae, James Michael</creator><creator>Wang, Shaomeng</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8782-6950</orcidid><orcidid>https://orcid.org/0000-0003-2239-5149</orcidid></search><sort><creationdate>20230713</creationdate><title>Targeting the Estrogen Receptor for the Treatment of Breast Cancer: Recent Advances and Challenges</title><author>Rej, Rohan Kalyan ; Acharyya, Ranjan Kumar ; Rae, James Michael ; Wang, Shaomeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a394t-fc546f17b21f8f40845d94338cc1c0b1ccfc71f3c22f0c7bdb36d9f37f5c62223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aromatase Inhibitors - pharmacology</topic><topic>Aromatase Inhibitors - therapeutic use</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Estrogen Antagonists - therapeutic use</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Selective Estrogen Receptor Modulators - pharmacology</topic><topic>Selective Estrogen Receptor Modulators - therapeutic use</topic><topic>Tamoxifen - pharmacology</topic><topic>Tamoxifen - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rej, Rohan Kalyan</creatorcontrib><creatorcontrib>Acharyya, Ranjan Kumar</creatorcontrib><creatorcontrib>Rae, James Michael</creatorcontrib><creatorcontrib>Wang, Shaomeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rej, Rohan Kalyan</au><au>Acharyya, Ranjan Kumar</au><au>Rae, James Michael</au><au>Wang, Shaomeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting the Estrogen Receptor for the Treatment of Breast Cancer: Recent Advances and Challenges</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2023-07-13</date><risdate>2023</risdate><volume>66</volume><issue>13</issue><spage>8339</spage><epage>8381</epage><pages>8339-8381</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>Estrogen receptor alpha (ERα) is a well-established therapeutic target for the treatment of ER-positive (ER+) breast cancers. Despite the tremendous successes achieved with tamoxifen, a selective ER modulator, and aromatase inhibitors (AIs), resistance to these therapies is a major clinical problem. Therefore, induced protein degradation and covalent inhibition have been pursued as new therapeutic approaches to target ERα. This Perspective summarizes recent progress in the discovery and development of oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), and proteolysis targeting chimera (PROTAC) ER degraders. We focus on those compounds which have been advanced into clinical development.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>37377342</pmid><doi>10.1021/acs.jmedchem.3c00136</doi><tpages>43</tpages><orcidid>https://orcid.org/0000-0002-8782-6950</orcidid><orcidid>https://orcid.org/0000-0003-2239-5149</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2023-07, Vol.66 (13), p.8339-8381 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2830671932 |
| source | ACS Publications; MEDLINE |
| subjects | Aromatase Inhibitors - pharmacology Aromatase Inhibitors - therapeutic use Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Estrogen Antagonists - therapeutic use Estrogen Receptor alpha - metabolism Female Humans Receptors, Estrogen - metabolism Selective Estrogen Receptor Modulators - pharmacology Selective Estrogen Receptor Modulators - therapeutic use Tamoxifen - pharmacology Tamoxifen - therapeutic use |
| title | Targeting the Estrogen Receptor for the Treatment of Breast Cancer: Recent Advances and Challenges |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T11%3A13%3A41IST&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=Targeting%20the%20Estrogen%20Receptor%20for%20the%20Treatment%20of%20Breast%20Cancer:%20Recent%20Advances%20and%20Challenges&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Rej,%20Rohan%20Kalyan&rft.date=2023-07-13&rft.volume=66&rft.issue=13&rft.spage=8339&rft.epage=8381&rft.pages=8339-8381&rft.issn=0022-2623&rft.eissn=1520-4804&rft_id=info:doi/10.1021/acs.jmedchem.3c00136&rft_dat=%3Cproquest_cross%3E2830671932%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2830671932&rft_id=info:pmid/37377342&rfr_iscdi=true |