Article(id=1198652615572681503, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1198652605778985059, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2023-0553, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1682870400000, receivedDateStr=2023-05-01, revisedDate=1689177600000, revisedDateStr=2023-07-13, acceptedDate=null, acceptedDateStr=null, onlineDate=1763710653441, onlineDateStr=2025-11-21, pubDate=1691769600000, pubDateStr=2023-08-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763710653441, onlineIssueDateStr=2025-11-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763710653441, creator=13701087609, updateTime=1763710653441, updator=13701087609, issue=Issue{id=1198652605778985059, tenantId=1146029695717560320, journalId=1189982191388893191, year='2023', volume='58', issue='8', pageStart='0', pageEnd='2540', issueExtLink='null', onlineDate='null', pubDate='1691769600000', pubDateStr='2023-08-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1763710651106, creator='13701087609', updateTime=1763710739504, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1198652976601596347, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1198652605778985059, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1198652976601596348, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1198652605778985059, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2193, endPage=2202, ext={EN=ArticleExt(id=1198652616088580921, articleId=1198652615572681503, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Research progress in controllable proteolysis targeting chimeras, columnId=null, journalTitle=Acta Pharmaceutica Sinica, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Proteolysis targeting chimeras (PROTACs) is an innovative technique in targeted protein degradation. PROTACs is a heterobifunctional molecule which can bind to the E3 ligase and target protein to form a ubiquitination complex, resulting in the ubiquitin-proteasome system dependent degradation of target protein. PROTACs has been regarded as the promising method in drug discovery campaign, for its high commonality, potent degradation activity and unique selectivity profile. However, the catalytic mechanism also induces the uncontrollable protein degradation risk. Controllable PROTACs contain the responsive element in the molecular entity. In certain conditions, the element can be triggered to activate or terminate the degradation event. In this review, we will briefly summarize the strategies in controllable PROTACs and describe the representative examples according to the responsive mechanism. We hope this review could provide some insight into the further development of controllable PROTACs.
, authors=null, authorsList=Yi MOU, Shuai WEN, Yan WANG, Zheng-yu JIANG, authorCompany=null, correspAuthors=Zheng-yu JIANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2023 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1198652623034347814, articleId=1198652615572681503, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=可控性蛋白降解靶向嵌合体(PROTACs) 技术研究进展, columnId=1190335349655180086, journalTitle=药学学报, columnName=综述, runingTitle=null, highlight=null, articleAbstract=
蛋白降解靶向嵌合体(PROTACs) 是一类新型蛋白降解技术, 能同时结合E3连接酶与疾病相关蛋白, 利用内源性泛素-蛋白酶体系降解靶蛋白。PROTACs具有较佳的通用性、较强的蛋白降解活性和较好的目的蛋白选择性, 成为靶向蛋白降解领域的热点技术, 但具有降解不受控的风险。可控PROTACs引入了特定的刺激响应触发元件, 在特定的响应条件下可被触发, 产生/终止后续的蛋白质降解效应。本文概述了可控PROTACs设计策略, 并按照相应机制不同对代表化合物和研究进展进行了介绍, 从而为可控PROTACs的研究提供借鉴和思路。
, authors=null, authorsList=牟伊, 文帅, 王燕, 姜正羽, authorCompany=null, correspAuthors=姜正羽, authorNote=null, correspAuthorsNote=
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1, address=1. College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou 225300, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1198960102796522495, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, authorId=1198960102494532581, language=CN, stringName=王燕, firstName=燕, middleName=null, lastName=王, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=
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2, *, address=2. Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1198960103199174689, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, authorId=1198960102922350602, language=CN, stringName=姜正羽, firstName=正羽, middleName=null, lastName=姜, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=
2, *, address=2.中国药科大学药学院, 江苏省药物分子设计与成药性优化重点实验室, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1198960101127189351, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, xref=null, ext=[AuthorCompanyExt(id=1198960101131383655, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, companyId=1198960101127189351, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1198960101143966569, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, companyId=1198960101127189351, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.中国药科大学药学院, 江苏省药物分子设计与成药性优化重点实验室, 江苏 南京 210009)])])], keywords=[Keyword(id=1198960103509553205, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, orderNo=1, keyword=proteolysis targeting chimeras), Keyword(id=1198960103677325373, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, orderNo=2, keyword=targeted protein degradation), Keyword(id=1198960103857680461, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, orderNo=3, keyword=controllable proteolysis targeting chimeras), Keyword(id=1198960104071589977, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, orderNo=1, keyword=蛋白降解靶向嵌合体), Keyword(id=1198960104189030497, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, orderNo=2, keyword=靶向蛋白降解), Keyword(id=1198960104319053931, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, orderNo=3, keyword=可控性蛋白降解靶向嵌合体)], refs=[Reference(id=1198960110086222342, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, doi=10.1016/j.molcel.2020.01.010, pmid=null, pmcid=null, year=2020, volume=77, issue=null, pageStart=446, pageEnd=460, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=null, journalName=Mol Cell, refType=null, unstructuredReference=Verma R, Mohl D, Deshaies RJ. Harnessing the power of proteolysis for targeted protein inactivation[J].
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145: 385-391., articleTitle=Radiotherapy-triggered proteolysis targeting chimera prodrug activation in tumors, refAbstract=null)], funds=[Fund(id=1198960109553545686, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, awardId=21KJB350008, language=CN, fundingSource=江苏省高校自然科学基金(21KJB350008), fundOrder=null, country=null), Fund(id=1198960109666791899, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, awardId=TN202135, language=CN, fundingSource=泰州市社会发展项目(TN202135), fundOrder=null, country=null), Fund(id=1198960109830369775, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, awardId=YY-110, language=CN, fundingSource=江苏省“六大人才高峰”资助(YY-110), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1198960100913279817, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, xref=null, ext=[AuthorCompanyExt(id=1198960100938445647, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, companyId=1198960100913279817, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou 225300, China), AuthorCompanyExt(id=1198960100959417172, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, companyId=1198960100913279817, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.泰州学院医药与化学化工学院, 江苏 泰州 225300)]), AuthorCompany(id=1198960101127189351, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, xref=null, ext=[AuthorCompanyExt(id=1198960101131383655, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, companyId=1198960101127189351, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1198960101143966569, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, companyId=1198960101127189351, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.中国药科大学药学院, 江苏省药物分子设计与成药性优化重点实验室, 江苏 南京 210009)])], figs=[ArticleFig(id=1198960104742678659, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=wwBjki71VgH+nGy3ODR9eQ==, figureFileBig=CmevEigAtrqq+muAKk1lsA==, tableContent=null), ArticleFig(id=1198960104939810966, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 1, caption=
The mechanism of PROTACs. PROTACs consists of three parts: target protein ligand, E3 ligase ligand and "linker" structure that connects the two ligands. PROTACs binds to the target protein and E3 ligase respectively through ligands at both ends to form a stable terpolymer complex, which labels the target protein for ubiquitination, and the ubiquitinated target protein is then recognized and degraded by the proteasome in the cell. PROTACs: Proteolysis targeting chimeras , figureFileSmall=wwBjki71VgH+nGy3ODR9eQ==, figureFileBig=CmevEigAtrqq+muAKk1lsA==, tableContent=null), ArticleFig(id=1198960105266966696, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=SwYBX6HxiWE8kjbpZ+TG7Q==, figureFileBig=2DBjmHvOaPiOV8jgh6Vg8A==, tableContent=null), ArticleFig(id=1198960105426350257, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 2, caption=
The mechanism of controlled PROTACs. The development strategy of controllable-PROTACs are mainly to block key binding sites in molecules with different stimulus response fragments (cage) to make the molecules lose degradation activity. Controllable-PROTACs are activated under specific response conditions to produce subsequent protein degradation effects , figureFileSmall=SwYBX6HxiWE8kjbpZ+TG7Q==, figureFileBig=2DBjmHvOaPiOV8jgh6Vg8A==, tableContent=null), ArticleFig(id=1198960105564762296, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=SyJFAr4LJJly4txMlUroMA==, figureFileBig=SJxjY5pjPujTBqrOLxmq+g==, tableContent=null), ArticleFig(id=1198960105694785730, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 3, caption=
Commonly used photocleavable protecting groups , figureFileSmall=SyJFAr4LJJly4txMlUroMA==, figureFileBig=SJxjY5pjPujTBqrOLxmq+g==, tableContent=null), ArticleFig(id=1198960105887723727, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=3uFHhSclSaOqYMGTOEORVA==, figureFileBig=uVfVHmtjAV9l7OLIlfWxIQ==, tableContent=null), ArticleFig(id=1198960106072273109, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 4, caption=
The chemical structures of pc-PROTACs and the release of pc-PROTAC1 , figureFileSmall=3uFHhSclSaOqYMGTOEORVA==, figureFileBig=uVfVHmtjAV9l7OLIlfWxIQ==, tableContent=null), ArticleFig(id=1198960106240045282, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=FmpZOBXGTrSFMOGOf9E6qw==, figureFileBig=K7UTZi5QXb/bWj0RcHwIHA==, tableContent=null), ArticleFig(id=1198960106416206058, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 5, caption=
The chemical structures of opto-PROTACs , figureFileSmall=FmpZOBXGTrSFMOGOf9E6qw==, figureFileBig=K7UTZi5QXb/bWj0RcHwIHA==, tableContent=null), ArticleFig(id=1198960106558812401, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=TZcLmiU4n564tLT8dfFkjg==, figureFileBig=aYlc8tfPVkcezjURPvCBDw==, tableContent=null), ArticleFig(id=1198960106672058618, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 6, caption=
The chemical structure of PROTAC3 , figureFileSmall=TZcLmiU4n564tLT8dfFkjg==, figureFileBig=aYlc8tfPVkcezjURPvCBDw==, tableContent=null), ArticleFig(id=1198960106785304835, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=VtbLss7e9cKvDIc2YR2ssg==, figureFileBig=UcODREpdXI9BxcfQ01e6+A==, tableContent=null), ArticleFig(id=1198960106948882701, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 7, caption=
The chemical structures of DEACM-caged ERRα PROTAC2 and NPOM-caged BRD4 PROTAC4 , figureFileSmall=VtbLss7e9cKvDIc2YR2ssg==, figureFileBig=UcODREpdXI9BxcfQ01e6+A==, tableContent=null), ArticleFig(id=1198960107099877656, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=kXhy0K5sZ2+9D6/grqJtwg==, figureFileBig=xidQ1gXVhLrpOb6x57Pz0w==, tableContent=null), ArticleFig(id=1198960107255066905, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 8, caption=
The chemical structures and release mechanism of PROTAC-I-3, PROTAC -Ⅱ-5 and PROTAC-Ⅱ-6 , figureFileSmall=kXhy0K5sZ2+9D6/grqJtwg==, figureFileBig=xidQ1gXVhLrpOb6x57Pz0w==, tableContent=null), ArticleFig(id=1198960107456393512, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=TfBsPU08MWp2dfknI/mfiQ==, figureFileBig=cWpsx9heo8pV1k6Y5RaQww==, tableContent=null), ArticleFig(id=1198960107594805553, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 9, caption=
The chemical structure and release mechanism of photoPROTAC-1 , figureFileSmall=TfBsPU08MWp2dfknI/mfiQ==, figureFileBig=cWpsx9heo8pV1k6Y5RaQww==, tableContent=null), ArticleFig(id=1198960107708051772, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=bItzH/DM1Mei1BUpZX/o1Q==, figureFileBig=YcAISt/0hZ/RbIadJ91aNw==, tableContent=null), ArticleFig(id=1198960107804520769, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 10, caption=
The chemical structures of Azo-PROTACs , figureFileSmall=bItzH/DM1Mei1BUpZX/o1Q==, figureFileBig=YcAISt/0hZ/RbIadJ91aNw==, tableContent=null), ArticleFig(id=1198960107913572682, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=rYz9jLEe4doYqOwJGDdU1w==, figureFileBig=oSrhFZe0xtwuW59qNTkKyg==, tableContent=null), ArticleFig(id=1198960108039401807, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 11, caption=
The chemical structures of Tz-PROTACs , figureFileSmall=rYz9jLEe4doYqOwJGDdU1w==, figureFileBig=oSrhFZe0xtwuW59qNTkKyg==, tableContent=null), ArticleFig(id=1198960108177813848, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=oWpioWuLKCGkNzPR4pnTag==, figureFileBig=W9ZAYENo+RxsSRc/0Npuyg==, tableContent=null), ArticleFig(id=1198960108379140459, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 12, caption=
The chemical structures of Ha-PROTACs , figureFileSmall=oWpioWuLKCGkNzPR4pnTag==, figureFileBig=W9ZAYENo+RxsSRc/0Npuyg==, tableContent=null), ArticleFig(id=1198960108559495547, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=jFJksRxsJMMCIcwAGmcC7g==, figureFileBig=2ftqT/gZ6KXxGhbJRfDVbw==, tableContent=null), ArticleFig(id=1198960108752433545, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 13, caption=
The chemical structures of NQO1-PROTAC and ROS-PROTAC , figureFileSmall=jFJksRxsJMMCIcwAGmcC7g==, figureFileBig=2ftqT/gZ6KXxGhbJRfDVbw==, tableContent=null), ArticleFig(id=1198960108899234196, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=wn/AjzutyGx0pwjwekw34Q==, figureFileBig=g2GhIv+s/98d0V572A+l5Q==, tableContent=null), ArticleFig(id=1198960109016674718, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 14, caption=
The chemical structure of FA-S2-POMA , figureFileSmall=wn/AjzutyGx0pwjwekw34Q==, figureFileBig=g2GhIv+s/98d0V572A+l5Q==, tableContent=null), ArticleFig(id=1198960109163475374, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=EN, label=null, caption=null, figureFileSmall=9lU9R4Qi6fA6Ajo90mG2rw==, figureFileBig=DV4WlMa/KtuWDYUceYqOpA==, tableContent=null), ArticleFig(id=1198960109293498811, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1198652615572681503, language=CN, label=Figure 15, caption=
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