ACS Central Science最新文献

筛选
英文 中文
DCAF16-Based Covalent Degradative Handles for the Modular Design of Degraders 基于dcaf16的共价降解手柄用于降解器的模块化设计。
IF 10.4 1区 化学
ACS Central Science Pub Date : 2025-06-26 DOI: 10.1021/acscentsci.5c00959
Lauren M. Orr, Sydney J. Tomlinson, Hannah R. Grupe, Melissa Lim, Emily Ho, Halime Yilmaz, Grace Zhou, Barbara Leon, James A. Olzmann* and Daniel K. Nomura*, 
{"title":"DCAF16-Based Covalent Degradative Handles for the Modular Design of Degraders","authors":"Lauren M. Orr,&nbsp;Sydney J. Tomlinson,&nbsp;Hannah R. Grupe,&nbsp;Melissa Lim,&nbsp;Emily Ho,&nbsp;Halime Yilmaz,&nbsp;Grace Zhou,&nbsp;Barbara Leon,&nbsp;James A. Olzmann* and Daniel K. Nomura*,&nbsp;","doi":"10.1021/acscentsci.5c00959","DOIUrl":"10.1021/acscentsci.5c00959","url":null,"abstract":"<p >While targeted protein degradation is a powerful strategy for eliminating disease-causing proteins, the rational design of monovalent or molecular glue degraders remains challenging. In this study, we generated a library of BET-domain inhibitor JQ1 analogs bearing elaborated electrophilic handles to identify permissive covalent degradative handles and E3 ligase pairs. We identified an elaborated fumaramide handle that, when appended onto JQ1, led to the proteasome-dependent degradation of BRD4. We revealed that the E3 ubiquitin ligase CUL4<sup>DCAF16</sup>─a common E3 ligase target of electrophilic degraders─was responsible for BRD4 loss by covalently targeting C173 on DCAF16. While this original fumaramide handle was not permissive to the degradation of other neo-substrates, a truncated version of this handle attached to JQ1 was still capable of degrading BRD4, now through targeting both C173 and C178. This truncated fumaramide handle, when appended to various protein targeting ligands, was also more permissive in degrading other neo-substrates, including CDK4/6, SMARCA2/4, the androgen receptor (AR), as well as the undruggable AR truncation variant AR-V7. We have identified a unique DCAF16-targeting covalent degradative handle that can be transplanted across several protein-targeting ligands to induce the degradation of their respective targets for the modular design of monovalent or bifunctional degraders.</p><p >We have discovered a covalent fumaramide-based degradative handle that acts through targeting C173 and C178 on the E3 ligase DCAF16 for the modular design of monovalent and bifunctional degraders.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1207–1217"},"PeriodicalIF":10.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Miao Chen,  and , Guangbin Dong*, 
{"title":"","authors":"Miao Chen,&nbsp; and ,&nbsp;Guangbin Dong*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Louisa Dalton, 
{"title":"","authors":"Louisa Dalton,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Jianghan Tian, Beiping Luo, Aidan Rafferty, Allen E. Haddrell, Ulrich K. Krieger and Jonathan P. Reid*, 
{"title":"","authors":"Jianghan Tian,&nbsp;Beiping Luo,&nbsp;Aidan Rafferty,&nbsp;Allen E. Haddrell,&nbsp;Ulrich K. Krieger and Jonathan P. Reid*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144430092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Jared Cason Head,  and , Syed Muhammad Usama​, 
{"title":"","authors":"Jared Cason Head,&nbsp; and ,&nbsp;Syed Muhammad Usama​,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00958","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Keldy S. Mason, Ji-Won Kim, Elizabeth A. Recker, Jenna M. Nymick, Mingyu Shi, Franz A. Stolpen, Jaechul Ju and Zachariah A. Page*, 
{"title":"","authors":"Keldy S. Mason,&nbsp;Ji-Won Kim,&nbsp;Elizabeth A. Recker,&nbsp;Jenna M. Nymick,&nbsp;Mingyu Shi,&nbsp;Franz A. Stolpen,&nbsp;Jaechul Ju and Zachariah A. Page*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144430093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Alan H. Weible,  and , Xiaoguang Wang​, 
{"title":"","authors":"Alan H. Weible,&nbsp; and ,&nbsp;Xiaoguang Wang​,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00983","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Aishanee Sur,  and , David C. Powers*, 
{"title":"","authors":"Aishanee Sur,&nbsp; and ,&nbsp;David C. Powers*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144430095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Catalyzing Chemistry Innovation: How Emerging Technologies Are Transforming the Chemical Industry 催化化学创新:新兴技术如何改变化学工业。
IF 10.4 1区 化学
ACS Central Science Pub Date : 2025-06-25 DOI: 10.1021/acscentsci.5c00530
F. Gomollón-Bel,  and , J. García-Martínez​, 
{"title":"Catalyzing Chemistry Innovation: How Emerging Technologies Are Transforming the Chemical Industry","authors":"F. Gomollón-Bel,&nbsp; and ,&nbsp;J. García-Martínez​,&nbsp;","doi":"10.1021/acscentsci.5c00530","DOIUrl":"10.1021/acscentsci.5c00530","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"819–822"},"PeriodicalIF":10.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-06-25
Ruonan Wang, Zhongyi Jian, Yanlian Yang, Chen Wang, Lanlan Yu*, Mingzhan Wang* and Chenxuan Wang*, 
{"title":"","authors":"Ruonan Wang,&nbsp;Zhongyi Jian,&nbsp;Yanlian Yang,&nbsp;Chen Wang,&nbsp;Lanlan Yu*,&nbsp;Mingzhan Wang* and Chenxuan Wang*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"2305–2315 XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信