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Development of Chemical Tools for the Human YEATS Domain. 人类领域化学工具的发展。
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-11 DOI: 10.1021/acschembio.5c00349
Xuejiao Shirley Guo, Abdalrahman Khalifa, Karthik Selvam, Tatiana G Kutateladze, Wenshe Ray Liu
{"title":"Development of Chemical Tools for the Human YEATS Domain.","authors":"Xuejiao Shirley Guo, Abdalrahman Khalifa, Karthik Selvam, Tatiana G Kutateladze, Wenshe Ray Liu","doi":"10.1021/acschembio.5c00349","DOIUrl":"https://doi.org/10.1021/acschembio.5c00349","url":null,"abstract":"<p><p>The YEATS domain is an evolutionarily conserved epigenetic reader that specifically recognizes post-translational lysine acylation on histone tails and plays a crucial role in chromatin remodeling and transcriptional regulation. Four human YEATS domain-containing proteins, ENL, AF9, YEATS2, and GAS41, have been implicated in the pathogenesis of various malignancies. This review provides an overview of the structural basis for the YEATS domain's recognition of diverse acyllysine post-translational modifications and discusses the disease-related consequences of aberrant YEATS activity. Emphasis is placed on recent progress in the development of chemical modulators, including peptide-based inhibitors, small molecules, and proteolysis-targeting chimeras (PROTACs), that represent promising strategies for the selective targeting of YEATS domains. These developments underscore the potential of YEATS-directed therapies in epigenetic drug discovery.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chemical Probe Discovery for DEAD-Box RNA-Binding Protein DDX21 Using Small-Molecule Microarrays. 利用小分子芯片发现DEAD-Box rna结合蛋白DDX21的化学探针。
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-10 DOI: 10.1021/acschembio.5c00302
Toshihiko Aiba, Eliezer Calo, Angela N Koehler
{"title":"Chemical Probe Discovery for DEAD-Box RNA-Binding Protein DDX21 Using Small-Molecule Microarrays.","authors":"Toshihiko Aiba, Eliezer Calo, Angela N Koehler","doi":"10.1021/acschembio.5c00302","DOIUrl":"https://doi.org/10.1021/acschembio.5c00302","url":null,"abstract":"<p><p>The DEAD-box family of ATPases plays a critical role in nearly all stages of RNA metabolism, from transcription to degradation, and serves as a major regulator of biomolecular condensates. Dysregulation of DEAD-box proteins is well-established in a variety of diseases, including cancer and neurodegenerative disorders, making them attractive therapeutic targets. However, their classification as \"undruggable\" has historically hindered small-molecule-based modulation. In this study, we focus on DDX21, a member of the DEAD-box family involved in ribosome biogenesis and transcription regulation. As a proof of concept for targeting such RNA-binding proteins, we developed a lysate-based small-molecule microarray platform to identify compounds that directly bind DDX21. This screen led to the discovery of KI-DX-014, a small-molecule compound capable of inhibiting the interaction of DDX21 with RNA. KI-DX-014 modulated the RNA-dependent functions of DDX21, including its ATPase activity and biomolecular condensate formation. Furthermore, KI-DX-014 attenuated the DDX21-dependent release of P-TEFb from the 7SK snRNP complex <i>in vitro</i>, suppressed P-TEFb-dependent phosphorylation of the RNA polymerase II CTD, and induced developmental defects in zebrafish embryos. These findings reveal a previously unexploited therapeutic avenue and establish KI-DX-014 as a chemical probe for dissecting the biological functions of DDX21 in both normal physiology and disease states.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human PTGR2 Inactivation Alters Eicosanoid Metabolism and Cytokine Response of Inflammatory Macrophages. 人PTGR2失活改变炎性巨噬细胞的类二十烷代谢和细胞因子反应。
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20 Epub Date: 2025-05-19 DOI: 10.1021/acschembio.5c00231
Michael W Founds, Olivia L Murtagh, R Justin Grams, Zhihong Li, Anthony M Ciancone, Robert J Seal, Ku-Lung Hsu
{"title":"Human PTGR2 Inactivation Alters Eicosanoid Metabolism and Cytokine Response of Inflammatory Macrophages.","authors":"Michael W Founds, Olivia L Murtagh, R Justin Grams, Zhihong Li, Anthony M Ciancone, Robert J Seal, Ku-Lung Hsu","doi":"10.1021/acschembio.5c00231","DOIUrl":"10.1021/acschembio.5c00231","url":null,"abstract":"<p><p>Prostaglandin reductase 2 (PTGR2) regulates inflammatory lipid signaling through the metabolism of the PGE2 metabolite 15-keto-PGE<sub>2</sub>. PTGR2 inhibitors have been reported but whether small molecule inactivation can recapitulate the anti-inflammatory phenotype observed in PTGR2 knockout systems has not been explored. Here, we disclose an optimized sulfonyl triazole (SuTEx) inhibitor of human PTGR2 that blocks biochemical activity by liganding the noncatalytic tyrosines Y100 and Y265 in the active site. Quantitative and multiplexed chemoproteomics verified covalent engagement of endogenous PTGR2 in THP1 macrophages with moderate proteome-wide selectivity. PTGR2 inactivation with the SuTEx inhibitor resulted in suppression of secreted inflammatory lipids and TNF-α in lipopolysaccharide (LPS)-stimulated macrophages. Collectively, our findings identify a potent covalent inhibitor of human PTGR2 that can serve as a tool compound for exploring lipid metabolism and signaling in macrophages.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1426-1434"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20
Severin Lechner*, Shuyao Sha, Jigar Paras Sethiya, Patrycja Szczupak, Rafal Dolot, Santosh Lomada, Amirhossein Sakhteman, Johanna Tushaus, Polina Prokofeva, Michael Krauss, Ferdinand Breu, Katharina Vögerl, Martin Morgenstern, Martin Hraběde Angelis, Volker Haucke, Thomas Wieland, Carston Wagner, Guillaume Médard, Franz Bracher and Bernhard Kuster*, 
{"title":"","authors":"Severin Lechner*,&nbsp;Shuyao Sha,&nbsp;Jigar Paras Sethiya,&nbsp;Patrycja Szczupak,&nbsp;Rafal Dolot,&nbsp;Santosh Lomada,&nbsp;Amirhossein Sakhteman,&nbsp;Johanna Tushaus,&nbsp;Polina Prokofeva,&nbsp;Michael Krauss,&nbsp;Ferdinand Breu,&nbsp;Katharina Vögerl,&nbsp;Martin Morgenstern,&nbsp;Martin Hraběde Angelis,&nbsp;Volker Haucke,&nbsp;Thomas Wieland,&nbsp;Carston Wagner,&nbsp;Guillaume Médard,&nbsp;Franz Bracher and Bernhard Kuster*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144343652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20
Xu-Dong Kong*, Meng-Jie Zhang and Christian Heinis*, 
{"title":"","authors":"Xu-Dong Kong*,&nbsp;Meng-Jie Zhang and Christian Heinis*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144343656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20
Ines Burkhart, Vivien Rose McKenney, Julia Wirmer-Bartoschek, J. Tassilo Grün, Alexander Heckel and Harald Schwalbe*, 
{"title":"","authors":"Ines Burkhart,&nbsp;Vivien Rose McKenney,&nbsp;Julia Wirmer-Bartoschek,&nbsp;J. Tassilo Grün,&nbsp;Alexander Heckel and Harald Schwalbe*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144469157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20
Jen Wagner, 
{"title":"","authors":"Jen Wagner,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144469159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20
Mercedes B. Fisk, Jocelyn Barrera Ramirez, Collin E. Merrick, Timothy A. Wencewicz and Andrew M. Gulick*, 
{"title":"","authors":"Mercedes B. Fisk,&nbsp;Jocelyn Barrera Ramirez,&nbsp;Collin E. Merrick,&nbsp;Timothy A. Wencewicz and Andrew M. Gulick*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144469167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20
Yixing Wang, Jessica D. Hess, Chen Wang, Lingzi Ma, Megan Luo, Jennifer Jossart, John J. Perry, David Kwon, Zhe Wang, Xinyu Pei, Changxian Shen, Yingying Wang, Mian Zhou, Holly Yin, David Horne, André Nussenzweig, Li Zheng* and Binghui Shen*, 
{"title":"","authors":"Yixing Wang,&nbsp;Jessica D. Hess,&nbsp;Chen Wang,&nbsp;Lingzi Ma,&nbsp;Megan Luo,&nbsp;Jennifer Jossart,&nbsp;John J. Perry,&nbsp;David Kwon,&nbsp;Zhe Wang,&nbsp;Xinyu Pei,&nbsp;Changxian Shen,&nbsp;Yingying Wang,&nbsp;Mian Zhou,&nbsp;Holly Yin,&nbsp;David Horne,&nbsp;André Nussenzweig,&nbsp;Li Zheng* and Binghui Shen*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144469169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-06-20
{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/cbv020i006_1949689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144469171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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