{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:08:29Z","timestamp":1792814909034,"version":"4.5.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1201400"],"award-info":[{"award-number":["2021YFF1201400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22220102001"],"award-info":[{"award-number":["22220102001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LD22H300001"],"award-info":[{"award-number":["LD22H300001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research and Development Program of China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Proteolysis targeting chimeras (PROTACs), which harness the ubiquitin-proteasome system to selectively induce targeted protein degradation, represent an emerging therapeutic technology with the potential to modulate traditional undruggable targets. Over the past few years, this technology has moved from academia to industry and more than 10 PROTACs have been advanced into clinical trials. However, designing potent PROTACs with desirable drug-like properties still remains a great challenge. Here, we report an updated online database, PROTAC-DB 2.0, which is a repository of structural and experimental data about PROTACs. In this 2nd release, we expanded the number of PROTACs to 3270, which corresponds to a 96% expansion over the first version. Meanwhile, the numbers of warheads (small molecules targeting the proteins of interest), linkers, and E3 ligands (small molecules recruiting E3 ligases) have increased to over 360, 1500\u00a0and 80, respectively. In addition, given the importance and the limited number of the crystal target-PROTAC-E3 ternary complex structures, we provide the predicted ternary complex structures for PROTACs with good degradation capability using our PROTAC-Model method. To further facilitate the analysis of PROTAC data, a new filtering strategy based on the E3 ligases is also added. PROTAC-DB 2.0 is available online at http:\/\/cadd.zju.edu.cn\/protacdb\/.<\/jats:p>","DOI":"10.1093\/nar\/gkac946","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T09:43:52Z","timestamp":1665481432000},"page":"D1367-D1372","source":"Crossref","is-referenced-by-count":143,"title":["PROTAC-DB 2.0: an updated database of PROTACs"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8476-7548","authenticated-orcid":false,"given":"Gaoqi","family":"Weng","sequence":"first","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"},{"name":"CarbonSilicon AI Technology Co. , Ltd, Hangzhou \u00a0310018, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyan","family":"Cai","sequence":"additional","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"},{"name":"Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-3785","authenticated-orcid":false,"given":"Dongsheng","family":"Cao","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University , Changsha \u00a0410004, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Du","sequence":"additional","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Shen","sequence":"additional","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafeng","family":"Deng","sequence":"additional","affiliation":[{"name":"CarbonSilicon AI Technology Co. , Ltd, Hangzhou \u00a0310018, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaojun","family":"He","sequence":"additional","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"},{"name":"Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7227-2580","authenticated-orcid":false,"given":"Tingjun","family":"Hou","sequence":"additional","affiliation":[{"name":"Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou \u00a0310058, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"2023010804261109500_B1","doi-asserted-by":"crossref","first-page":"8554","DOI":"10.1073\/pnas.141230798","article-title":"Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation","volume":"98","author":"Sakamoto","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2023010804261109500_B2","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1016\/j.bmcl.2008.07.114","article-title":"Targeted intracellular protein degradation induced by a small molecule: en route to chemical proteomics","volume":"18","author":"Schneekloth","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2023010804261109500_B3","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1021\/ja100691p","article-title":"Protein knockdown using methyl bestatin\u2212ligand hybrid molecules: design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins","volume":"132","author":"Itoh","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"2023010804261109500_B4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: the past is prologue","volume":"21","author":"Bekes","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023010804261109500_B5","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nchembio.1858","article-title":"Catalytic in vivo protein knockdown by small-molecule PROTACs","volume":"11","author":"Bondeson","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"2023010804261109500_B6","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41573-021-00245-x","article-title":"The PROTACtable genome","volume":"20","author":"Schneider","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023010804261109500_B7","doi-asserted-by":"crossref","first-page":"D1381","DOI":"10.1093\/nar\/gkaa807","article-title":"PROTAC-DB: an online database of PROTACs","volume":"49","author":"Weng","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2023010804261109500_B8","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1126\/science.aab1433","article-title":"Phthalimide conjugation as a strategy for in vivo target protein degradation","volume":"348","author":"Winter","year":"2015","journal-title":"Science"},{"key":"2023010804261109500_B9","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ccell.2019.10.002","article-title":"A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo","volume":"36","author":"Bai","year":"2019","journal-title":"Cancer Cell"},{"key":"2023010804261109500_B10","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1021\/acschembio.5b00216","article-title":"Selective small molecule induced degradation of the BET bromodomain protein BRD4","volume":"10","author":"Zengerle","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"2023010804261109500_B11","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.cell.2020.10.038","article-title":"Mapping the degradable kinome provides a resource for expedited degrader development","volume":"183","author":"Donovan","year":"2020","journal-title":"Cell"},{"key":"2023010804261109500_B12","doi-asserted-by":"crossref","first-page":"13487","DOI":"10.1021\/acs.jmedchem.1c00900","article-title":"Discovery of ARD-2585 as an exceptionally potent and orally active PROTAC degrader of androgen receptor for the treatment of advanced prostate cancer","volume":"64","author":"Xiang","year":"2021","journal-title":"J. Med. Chem."},{"key":"2023010804261109500_B13","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1021\/acs.jmedchem.8b01413","article-title":"Iterative design and optimization of initially inactive proteolysis targeting chimeras (PROTACs) identify VZ185 as a potent, fast, and selective von hippel-lindau (VHL) based dual degrader probe of BRD9 and BRD7","volume":"62","author":"Zoppi","year":"2019","journal-title":"J. Med. Chem."},{"key":"2023010804261109500_B14","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-021-04246-z","article-title":"Targeting SWI\/SNF ATPases in enhancer-addicted prostate cancer","volume":"601","author":"Xiao","year":"2022","journal-title":"Nature"},{"key":"2023010804261109500_B15","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41589-021-00765-y","article-title":"Discovery and resistance mechanism of a selective CDK12 degrader","volume":"17","author":"Jiang","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"2023010804261109500_B16","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1039\/C9MD00272C","article-title":"Developing degraders: principles and perspectives on design and chemical space","volume":"10","author":"Maple","year":"2019","journal-title":"Medchemcomm"},{"key":"2023010804261109500_B17","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.bmcl.2019.04.030","article-title":"Proteolysis targeting chimeras (PROTACs) in \u2018beyond rule-of-five\u2019 chemical space: recent progress and future challenges","volume":"29","author":"Edmondson","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2023010804261109500_B18","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/s41589-019-0362-y","article-title":"Development of targeted protein degradation therapeutics","volume":"15","author":"Chamberlain","year":"2019","journal-title":"Nat. Chem. 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