{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:16:33Z","timestamp":1793945793139,"version":"4.8.0"},"reference-count":122,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1302100"],"award-info":[{"award-number":["2021YFA1302100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1300200"],"award-info":[{"award-number":["2021YFA1300200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1300200,2021YFA1302100"],"award-info":[{"award-number":["2021YFA1300200,2021YFA1302100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFE0202200"],"award-info":[{"award-number":["2020YFE0202200"]}],"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":["82125034"],"award-info":[{"award-number":["82125034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330115"],"award-info":[{"award-number":["82330115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Science Bulletin"],"published-print":{"date-parts":[[2024,6]]},"DOI":"10.1016\/j.scib.2024.03.056","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T12:48:08Z","timestamp":1711716488000},"page":"1776-1797","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":108,"title":["Targeting the undruggables\u2014the power of protein degraders"],"prefix":"10.1016","volume":"69","author":[{"given":"Chao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangchen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunquan","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.scib.2024.03.056_b0005","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nrc.2017.36","article-title":"Drugging the \u2018undruggable\u2019 cancer targets","volume":"17","author":"Dang","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.scib.2024.03.056_b0010","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41392-023-01589-z","article-title":"Recent advances in targeting the \u201cundruggable\u201d proteins: From drug discovery to clinical trials","volume":"8","author":"Xie","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.scib.2024.03.056_b0015","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/17460441.2021.1969359","article-title":"Strategies for targeting undruggable targets","volume":"17","author":"Zhang","year":"2022","journal-title":"Expert Opin Drug Discov"},{"key":"10.1016\/j.scib.2024.03.056_b0020","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.13005\/bpj\/2277","article-title":"RNA-targeting therapy: A promising approach to reach non-druggable targets","volume":"14","author":"Zaafar","year":"2021","journal-title":"Biomed Pharmacol J"},{"key":"10.1016\/j.scib.2024.03.056_b0025","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1038\/s41401-021-00852-9","article-title":"Current strategies and progress for targeting the \u201cundruggable\u201d transcription factors","volume":"43","author":"Zhuang","year":"2022","journal-title":"Acta Pharmacol Sin"},{"key":"10.1016\/j.scib.2024.03.056_b0030","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41573-021-00199-0","article-title":"Advances in targeting \u2018undruggable\u2019 transcription factors with small molecules","volume":"20","author":"Henley","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.scib.2024.03.056_b0035","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41573-020-0068-6","article-title":"RAS-targeted therapies: Is the undruggable drugged?","volume":"19","author":"Moore","year":"2020","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.scib.2024.03.056_b0040","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/0889311X.2023.2208518","article-title":"Intrinsic disorder and flexibility in proteins: A challenge for structural biology and drug design","volume":"29","author":"Zanotti","year":"2023","journal-title":"Crystallogr Rev"},{"key":"10.1016\/j.scib.2024.03.056_b0045","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.tibs.2023.01.008","article-title":"Fragment-based drug discovery supports drugging \u2018undruggable\u2019 protein\u2013protein interactions","volume":"48","author":"Wang","year":"2023","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.scib.2024.03.056_b0050","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1021\/acs.accounts.6b00537","article-title":"Drugging the undruggable: Therapeutic potential of targeting protein tyrosine phosphatases","volume":"50","author":"Zhang","year":"2017","journal-title":"Acc Chem Res"},{"key":"10.1016\/j.scib.2024.03.056_b0055","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/s41573-019-0047-y","article-title":"Targeted protein degradation: Expanding the toolbox","volume":"18","author":"Schapira","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.scib.2024.03.056_b0060","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cbpa.2019.11.012","article-title":"Targeted protein degradation: Current and future challenges","volume":"56","author":"Hanzl","year":"2020","journal-title":"Curr Opin Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0065","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1021\/acs.jcim.3c00603","article-title":"Targeted protein degradation: Advances, challenges, and prospects for computational methods","volume":"63","author":"Mostofian","year":"2023","journal-title":"J Chem Inf Model"},{"key":"10.1016\/j.scib.2024.03.056_b0070","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41392-022-00966-4","article-title":"Targeted protein degradation: Mechanisms, strategies and application","volume":"7","author":"Zhao","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.scib.2024.03.056_b0075","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/s41568-021-00365-x","article-title":"Advancing targeted protein degradation for cancer therapy","volume":"21","author":"Dale","year":"2021","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.scib.2024.03.056_b0080","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":"B\u00e9k\u00e9s","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.scib.2024.03.056_b0085","doi-asserted-by":"crossref","first-page":"7066","DOI":"10.1039\/D2CS00220E","article-title":"Chemistries of bifunctional protac degraders","volume":"51","author":"Cao","year":"2022","journal-title":"Chem Soc Rev"},{"key":"10.1016\/j.scib.2024.03.056_b0090","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41392-019-0101-6","article-title":"Protacs: Great opportunities for academia and industry","volume":"4","author":"Sun","year":"2019","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.scib.2024.03.056_b0095","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41392-022-00999-9","article-title":"Protacs: Great opportunities for academia and industry (an update from 2020 to 2021)","volume":"7","author":"He","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.scib.2024.03.056_b0100","first-page":"409","article-title":"ROTACs targeting epigenetic proteins","volume":"2","author":"Zhang","year":"2023","journal-title":"Acta Mater Med"},{"key":"10.1016\/j.scib.2024.03.056_b0105","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.cell.2020.12.020","article-title":"The rise of molecular glues","volume":"184","author":"Schreiber","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.scib.2024.03.056_b0110","doi-asserted-by":"crossref","first-page":"9278","DOI":"10.1021\/acs.jmedchem.3c00449","article-title":"Molecular glue discovery: Current and future approaches","volume":"66","author":"Dewey","year":"2023","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115950","article-title":"Facilitating the development of molecular glues: Opportunities from serendipity and rational design","volume":"263","author":"Jiang","year":"2024","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0120","doi-asserted-by":"crossref","first-page":"10606","DOI":"10.1021\/acs.jmedchem.1c00895","article-title":"Molecular glues for targeted protein degradation: From serendipity to rational discovery","volume":"64","author":"Dong","year":"2021","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0125","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41589-021-00835-1","article-title":"Lysosome-targeting chimeras evolve","volume":"17","author":"Paulk","year":"2021","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0130","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.100647","article-title":"Major advances in targeted protein degradation: Protacs, lytacs, and madtacs","volume":"296","author":"Alabi","year":"2021","journal-title":"J Biol Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0135","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tips.2020.04.005","article-title":"Emerging new concepts of degrader technologies","volume":"41","author":"Ding","year":"2020","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.scib.2024.03.056_b0140","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.1039\/D2CS00141A","article-title":"Degrader-antibody conjugates","volume":"51","author":"Dragovich","year":"2022","journal-title":"Chem Soc Rev"},{"key":"10.1016\/j.scib.2024.03.056_b0145","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 USA"},{"key":"10.1016\/j.scib.2024.03.056_b0150","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK-STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.scib.2024.03.056_b0155","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrc1275","article-title":"The stats of cancer \u2014 new molecular targets come of age","volume":"4","author":"Yu","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.scib.2024.03.056_b0160","doi-asserted-by":"crossref","first-page":"11280","DOI":"10.1021\/acs.jmedchem.9b01530","article-title":"Structure-based discovery of SD-36 as a potent, selective, and efficacious PROTAC degrader of STAT3 protein","volume":"62","author":"Zhou","year":"2019","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0165","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1021\/acsmedchemlett.1c00155","article-title":"SD-91 as a potent and selective STAT3 degrader capable of achieving complete and long-lasting tumor regression","volume":"12","author":"Zhou","year":"2021","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.scib.2024.03.056_b0170","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/s41375-017-0005-9","article-title":"Pharmacologic inhibition of STAT5 in acute myeloid leukemia","volume":"32","author":"Wingelhofer","year":"2018","journal-title":"Leukemia"},{"key":"10.1016\/j.scib.2024.03.056_b0175","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3324\/haematol.2019.216986","article-title":"High activation of STAT5A drives peripheral T-cell lymphoma and leukemia","volume":"105","author":"Barbara","year":"2020","journal-title":"Haematologica"},{"key":"10.1016\/j.scib.2024.03.056_b0180","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41589-022-01248-4","article-title":"A selective small-molecule STAT5 protac degrader capable of achieving tumor regression in vivo","volume":"19","author":"Kaneshige","year":"2023","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0185","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2021.102154","article-title":"Myc as a target for cancer treatment","volume":"94","author":"Duffy","year":"2021","journal-title":"Cancer Treat Rev"},{"key":"10.1016\/j.scib.2024.03.056_b0190","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1158\/1538-7445.AM2022-5479","article-title":"Abstract 5479: Discovery and evaluation of GT19630, a c-Myc\/GSPT1 cereblon E3 ligase modulator (CELMoD), for targeting Myc-driven blood cancers and small cell lung cancers (SCLC)","volume":"82","author":"Ma","year":"2022","journal-title":"Cancer Res"},{"key":"10.1016\/j.scib.2024.03.056_b0195","doi-asserted-by":"crossref","first-page":"9334","DOI":"10.1021\/jacs.3c02619","article-title":"C-Myc-targeting PROTAC based on a TNA-DNA bivalent binder for combination therapy of triple-negative breast cancer","volume":"145","author":"Li","year":"2023","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.scib.2024.03.056_b0200","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1002\/jcp.30759","article-title":"NF-\u03baB as a regulator of cancer metastasis and therapy response: A focus on epithelial\u2013mesenchymal transition","volume":"237","author":"Mirzaei","year":"2022","journal-title":"J Cell Physiol"},{"key":"10.1016\/j.scib.2024.03.056_b0205","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1080\/15384101.2020.1801190","article-title":"The E2F1 transcription factor and RB tumor suppressor moonlight as DNA repair factors","volume":"19","author":"Manickavinayaham","year":"2020","journal-title":"Cell Cycle"},{"key":"10.1016\/j.scib.2024.03.056_b0210","doi-asserted-by":"crossref","first-page":"8902","DOI":"10.1021\/jacs.1c03852","article-title":"Tf-protacs enable targeted degradation of transcription factors","volume":"143","author":"Liu","year":"2021","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.scib.2024.03.056_b0215","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41419-023-06056-9","article-title":"Development of an interfering peptide M1\u201320 with potent anti-cancer effects by targeting FOXM1","volume":"14","author":"Bu","year":"2023","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.scib.2024.03.056_b0220","doi-asserted-by":"crossref","first-page":"17098","DOI":"10.1021\/acs.jmedchem.1c01069","article-title":"Targeting of the FOXM1\u00a0 oncoprotein by E3 ligase-assisted degradation","volume":"64","author":"Luo","year":"2021","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0225","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s13046-022-02483-2","article-title":"Peptide-based PROTAC degrader of FOXM1 suppresses cancer and decreases GLUT1 and PD-L1 expression","volume":"41","author":"Wang","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"10.1016\/j.scib.2024.03.056_b0230","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s13402-022-00698-1","article-title":"A comprehensive review of SHP2 and its role in cancer","volume":"45","author":"Asmamaw","year":"2022","journal-title":"Cell Oncol"},{"key":"10.1016\/j.scib.2024.03.056_b0235","doi-asserted-by":"crossref","first-page":"7510","DOI":"10.1021\/acs.jmedchem.0c00471","article-title":"Discovery of SHP2-D26 as a first, potent, and effective PROTAC degrader of SHP2 protein","volume":"63","author":"Wang","year":"2020","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0240","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.104788","article-title":"Novel protacs for degradation of SHP2 protein","volume":"110","author":"Zheng","year":"2021","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0245","doi-asserted-by":"crossref","first-page":"6947","DOI":"10.3390\/molecules28196947","article-title":"Discovery of a SHP2 degrader with in vivo anti-tumor activity","volume":"28","author":"Miao","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.scib.2024.03.056_b0250","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113341","article-title":"Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders","volume":"218","author":"Yang","year":"2021","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0255","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1021\/acs.biochem.1c00377","article-title":"Targeted degradation of the oncogenic phosphatase SHP2","volume":"60","author":"Vemulapalli","year":"2021","journal-title":"Biochemistry"},{"key":"10.1016\/j.scib.2024.03.056_b0260","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115124","article-title":"Annual review of KRAS inhibitors in 2022","volume":"249","author":"Wang","year":"2023","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0265","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.chembiol.2019.12.006","article-title":"Exploring targeted degradation strategy for oncogenic KRASG12C","volume":"27","author":"Zeng","year":"2020","journal-title":"Cell Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0270","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1021\/acscentsci.0c00411","article-title":"Targeted degradation of oncogenic KRASG12C by VHL-recruiting PROTACs","volume":"6","author":"Bond","year":"2020","journal-title":"ACS Cent Sci"},{"key":"10.1016\/j.scib.2024.03.056_b0275","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.114088","article-title":"Efficient targeted oncogenic KRASG12C degradation via first reversible-covalent PROTAC","volume":"230","author":"Yang","year":"2022","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0280","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.105447","article-title":"Discovery of KRas G12C-IN-3 and pomalidomide-based PROTACs as degraders of endogenous KRAS G12C with potent anticancer activity","volume":"117","author":"Li","year":"2021","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0285","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115857","article-title":"Discovery of highly potent and selective KRASG12C degraders by VHL-recruiting PROTACs for the treatment of tumors with KRASG12C-mutation","volume":"261","author":"Yang","year":"2023","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0290","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2023.117153","article-title":"Design, synthesis and biological evaluation of KRASG12C-PROTACs","volume":"78","author":"Zhang","year":"2023","journal-title":"Bioorg Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0295","article-title":"Targeting cancer with small molecule pan-KRAS degraders","author":"Johannes","year":"2023","journal-title":"bioRxiv."},{"key":"10.1016\/j.scib.2024.03.056_b0300","doi-asserted-by":"crossref","first-page":"5735","DOI":"10.1158\/1538-7445.AM2023-5735","article-title":"Abstract 5735: Novel KRAS G12D degrader ASP3082 demonstrates in vivo, dose-dependent KRAS degradation, KRAS pathway inhibition, and antitumor efficacy in multiple KRAS G12D-mutated cancer models","volume":"83","author":"Nagashima","year":"2023","journal-title":"Cancer Res"},{"key":"10.1016\/j.scib.2024.03.056_b0305","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/biof.1930","article-title":"Tau, tau kinases, and tauopathies: An updated overview","volume":"49","author":"Montalto","year":"2023","journal-title":"BioFactors"},{"key":"10.1016\/j.scib.2024.03.056_b0310","doi-asserted-by":"crossref","first-page":"5279","DOI":"10.7150\/thno.55680","article-title":"A novel small-molecule protac selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"10.1016\/j.scib.2024.03.056_b0315","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2022.801179","article-title":"Discovery and optimization of tau targeted protein degraders enabled by patient induced pluripotent stem cells-derived neuronal models of tauopathy","volume":"16","author":"Silva","year":"2022","journal-title":"Front Cell Neurosci"},{"key":"10.1016\/j.scib.2024.03.056_b0320","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.3390\/cells9122648","article-title":"Cyclin d1 in cancer: A molecular connection for cell cycle control, adhesion and invasion in tumor and stroma","volume":"9","author":"Montalto","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.scib.2024.03.056_b0325","doi-asserted-by":"crossref","first-page":"22622","DOI":"10.1021\/jacs.2c09255","article-title":"Bridged proteolysis targeting chimera (PROTAC) enables degradation of undruggable targets","volume":"144","author":"Xiong","year":"2022","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.scib.2024.03.056_b0330","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.3390\/cells9122565","article-title":"Pathological functions of LRRK2 in Parkinson\u2019s disease","volume":"9","author":"Jeong","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.scib.2024.03.056_b0335","doi-asserted-by":"crossref","first-page":"16930","DOI":"10.1021\/jacs.2c05499","article-title":"Discovery of XL01126: A potent, fast, cooperative, selective, orally bioavailable, and blood\u2013brain barrier penetrant PROTAC degrader of leucine-rich repeat kinase 2","volume":"144","author":"Liu","year":"2022","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.scib.2024.03.056_b0340","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104547","article-title":"Bcl-XL: A multifunctional anti-apoptotic protein","volume":"151","author":"Li","year":"2020","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.scib.2024.03.056_b0345","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1038\/s41591-019-0668-z","article-title":"A selective Bcl-XL protac degrader achieves safe and potent antitumor activity","volume":"25","author":"Khan","year":"2019","journal-title":"Nat Med"},{"key":"10.1016\/j.scib.2024.03.056_b0350","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0092-8674(91)90124-H","article-title":"Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes","volume":"66","author":"Liu","year":"1991","journal-title":"Cell"},{"key":"10.1016\/j.scib.2024.03.056_b0355","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0952-7915(93)90135-F","article-title":"Cyclosporin a and FK506: Molecular mechanisms of immunosuppression and probes for transplantation biology","volume":"5","author":"Bierer","year":"1993","journal-title":"Curr Opin Immunol"},{"key":"10.1016\/j.scib.2024.03.056_b0360","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1126\/science.273.5272.239","article-title":"Structure of the FKBP12-rapamycin complex interacting with binding domain of human frap","volume":"273","author":"Choi","year":"1996","journal-title":"Science"},{"key":"10.1016\/j.scib.2024.03.056_b0365","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nature18611","article-title":"A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase","volume":"535","author":"Matyskiela","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.scib.2024.03.056_b0370","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1021\/acschembio.0c00520","article-title":"Selective degradation of GSPT1 by cereblon modulators identified via a focused combinatorial library","volume":"15","author":"Powell","year":"2020","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0375","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1021\/acs.jmedchem.0c01489","article-title":"CC-90009: A cereblon E3 ligase modulating drug that promotes selective degradation of GSPT1 for the treatment of acute myeloid leukemia","volume":"64","author":"Hansen","year":"2021","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0380","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1021\/acs.jmedchem.0c01313","article-title":"Identification of potent, selective, and orally bioavailable small-molecule GSPT1\/2 degraders from a focused library of cereblon modulators","volume":"64","author":"Nishiguchi","year":"2021","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0385","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1021\/acschembio.7b00969","article-title":"Translation termination factor GSPT1 is a phenotypically relevant off-target of heterobifunctional phthalimide degraders","volume":"13","author":"Ishoey","year":"2018","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0390","doi-asserted-by":"crossref","first-page":"9471","DOI":"10.1021\/acs.jmedchem.9b00846","article-title":"Simple structural modifications converting a bona fide MDM2 PROTAC\u00a0 degrader into a molecular glue molecule: A cautionary tale in the design of PROTAC degraders","volume":"62","author":"Yang","year":"2019","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0395","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/s41422-021-00533-6","article-title":"Merging protac and molecular glue for degrading BTK and GSPT1\u00a0 proteins concurrently","volume":"31","author":"Yang","year":"2021","journal-title":"Cell Res"},{"key":"10.1016\/j.scib.2024.03.056_b0400","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1126\/science.1177319","article-title":"Identification of a primary target of thalidomide teratogenicity","volume":"327","author":"Ito","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.scib.2024.03.056_b0405","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.1244851","article-title":"Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells","volume":"343","author":"Kr\u00f6nke","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.scib.2024.03.056_b0410","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1126\/science.1244917","article-title":"The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins","volume":"343","author":"Lu","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.scib.2024.03.056_b0415","doi-asserted-by":"crossref","first-page":"eaat0572","DOI":"10.1126\/science.aat0572","article-title":"Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN","volume":"362","author":"Sievers","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.scib.2024.03.056_b0420","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1021\/acs.jmedchem.6b01921","article-title":"A cereblon modulator (CC-220) with improved degradation of Ikaros and Aiolos","volume":"61","author":"Matyskiela","year":"2018","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0425","doi-asserted-by":"crossref","first-page":"6648","DOI":"10.1021\/acs.jmedchem.9b01928","article-title":"Discovery of CRBN E3 ligase modulator CC-92480 for the treatment of relapsed and refractory multiple myeloma","volume":"63","author":"Hansen","year":"2020","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0430","doi-asserted-by":"crossref","first-page":"e38430","DOI":"10.7554\/eLife.38430","article-title":"Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome","volume":"7","author":"Donovan","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.scib.2024.03.056_b0435","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/s41589-019-0366-7","article-title":"P63 is a cereblon substrate involved in thalidomide teratogenicity","volume":"15","author":"Asatsuma-Okumura","year":"2019","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0440","article-title":"A selective small-molecule c-myc degrader potently regresses lethal c-myc overexpressing tumors","volume":"9","author":"Xu","year":"2022","journal-title":"Adv Sci"},{"key":"10.1016\/j.scib.2024.03.056_b0445","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1038\/s41467-021-24575-x","article-title":"A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion","volume":"12","author":"Sharma","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.scib.2024.03.056_b0450","doi-asserted-by":"crossref","DOI":"10.1038\/s41589-023-01521-0","article-title":"The eRF1 degrader SRI-41315 acts as a molecular glue at the ribosomal decoding center","author":"Coelho","year":"2024","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0455","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/s41420-021-00598-7","article-title":"RNA-binding protein 39: A promising therapeutic target for cancer","volume":"7","author":"Xu","year":"2021","journal-title":"Cell Death Discov"},{"key":"10.1016\/j.scib.2024.03.056_b0460","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nchembio.2363","article-title":"Selective degradation of splicing factor CAPER\u03b1 by anticancer sulfonamides","volume":"13","author":"Uehara","year":"2017","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0465","doi-asserted-by":"crossref","first-page":"eaal3755","DOI":"10.1126\/science.aal3755","article-title":"Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15","volume":"356","author":"Han","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.scib.2024.03.056_b0470","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41589-019-0378-3","article-title":"Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15","volume":"16","author":"Faust","year":"2020","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0475","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41589-019-0411-6","article-title":"Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex","volume":"16","author":"Bussiere","year":"2020","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0480","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1021\/acschembio.0c00674","article-title":"Cereblon modulators target ZBTB16 and its oncogenic fusion partners for degradation via distinct structural degrons","volume":"15","author":"Matyskiela","year":"2020","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0485","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s41589-020-0557-2","article-title":"Manumycin polyketides act as molecular glues between UBR7 and p53","volume":"16","author":"Isobe","year":"2020","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0490","doi-asserted-by":"crossref","first-page":"e59994","DOI":"10.7554\/eLife.59994","article-title":"Discovery of a molecular glue promoting CDK12-DDB1\u00a0 interaction to trigger cyclin k degradation","volume":"9","author":"Lv","year":"2020","journal-title":"eLife"},{"key":"10.1016\/j.scib.2024.03.056_b0495","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41586-020-2374-x","article-title":"The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K","volume":"585","author":"S\u0142abicki","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.scib.2024.03.056_b0500","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.chembiol.2023.02.008","article-title":"Chemoproteomics-enabled discovery of a covalent molecular glue degrader targeting NF-\u03baB","volume":"30","author":"King","year":"2023","journal-title":"Cell Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0505","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2022.104353","article-title":"Atypical E3 ligase ZFP91 promotes small-molecule-induced E2F2 transcription factor degradation for cancer therapy","volume":"86","author":"Liu","year":"2022","journal-title":"Ebiomedicine"},{"key":"10.1016\/j.scib.2024.03.056_b0510","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113425","article-title":"Development of MDM2 degraders based on ligands derived from UGI reactions: Lessons and discoveries","volume":"219","author":"Wang","year":"2021","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0515","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/s41586-020-2925-1","article-title":"Small-molecule-induced polymerization triggers degradation of BCL6","volume":"588","author":"S\u0142abicki","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.scib.2024.03.056_b0520","doi-asserted-by":"crossref","first-page":"eabi5797","DOI":"10.1126\/sciadv.abi5797","article-title":"Identification and optimization of molecular glue compounds that inhibit a noncovalent E2 enzyme\u2013ubiquitin complex","volume":"7","author":"St-Cyr","year":"2021","journal-title":"Sci Adv"},{"key":"10.1016\/j.scib.2024.03.056_b0525","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1038\/s41467-021-24495-w","article-title":"Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase","volume":"12","author":"Garvie","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.scib.2024.03.056_b0530","doi-asserted-by":"crossref","first-page":"eabh1486","DOI":"10.1126\/scitranslmed.abh1486","article-title":"Ubiquitination and degradation of sumo1 by small-molecule degraders extends survival of mice with patient-derived tumors","volume":"13","author":"Bellail","year":"2021","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.scib.2024.03.056_b0535","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/acs.jmedchem.2c01791","article-title":"Degrader-antibody conjugates: Emerging new modality","volume":"66","author":"Ki Bum Hong and Hongchan An","year":"2023","journal-title":"J Med Chem"},{"key":"10.1016\/j.scib.2024.03.056_b0540","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2019.126907","article-title":"Antibody-mediated delivery of chimeric protein degraders which target estrogen receptor alpha (ER\u03b1)","volume":"30","author":"Dragovich","year":"2020","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.scib.2024.03.056_b0545","unstructured":"Thompson PA, Edris B, Coburn CA, et al. Preparation of immunomodulatory and immunostimulatory antibody conjugates for use in treatment of cancer. WO2018227023 2018."},{"key":"10.1016\/j.scib.2024.03.056_b0550","volume":"WO2022020288","author":"Dragovich","year":"2022","journal-title":"Chimeric antibody-cide conjugated chemical inducers of degradation of BRM proteins and methods for treating BRM-dependent diseases such as cancer"},{"key":"10.1016\/j.scib.2024.03.056_b0555","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1158\/1538-7445.AM2022-3933","article-title":"Abstract 3933: ORM-5029: A first-in-class targeted protein degradation therapy using antibody neodegrader conjugate (ANDC) for HER2-expressing breast cancer","volume":"82","author":"Palacino","year":"2022","journal-title":"Cancer Res"},{"key":"10.1016\/j.scib.2024.03.056_b0560","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41586-020-2545-9","article-title":"Lysosome-targeting chimaeras for degradation of extracellular proteins","volume":"584","author":"Banik","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.scib.2024.03.056_b0565","doi-asserted-by":"crossref","first-page":"eadf6249","DOI":"10.1126\/science.adf6249","article-title":"Elucidating the cellular determinants of targeted membrane protein degradation by lysosome-targeting chimeras","volume":"382","author":"Ahn","year":"2023","journal-title":"Science"},{"key":"10.1016\/j.scib.2024.03.056_b0570","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/s41589-021-00770-1","article-title":"Lytacs that engage the asialoglycoprotein receptor for targeted protein degradation","volume":"17","author":"Ahn","year":"2021","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0575","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/s41589-021-00851-1","article-title":"Bifunctional small molecules that mediate the degradation of extracellular proteins","volume":"17","author":"Caianiello","year":"2021","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.scib.2024.03.056_b0580","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/acscentsci.1c00146","article-title":"Development of triantennary n-acetylgalactosamine conjugates as degraders for extracellular proteins","volume":"7","author":"Zhou","year":"2021","journal-title":"ACS Cent Sci"},{"key":"10.1016\/j.scib.2024.03.056_b0585","article-title":"Aptamer-lytacs for targeted degradation of extracellular and membrane proteins","volume":"62","author":"Wu","year":"2023","journal-title":"Angew Chem Int Ed Engl"},{"key":"10.1016\/j.scib.2024.03.056_b0590","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.molcel.2019.09.009","article-title":"AUTACs: Cargo-specific degraders using selective autophagy","volume":"76","author":"Takahashi","year":"2019","journal-title":"Mol Cell"},{"key":"10.1016\/j.scib.2024.03.056_b0595","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-019-1722-1","article-title":"Allele-selective lowering of mutant HTT protein by HTT\u2013LC3 linker compounds","volume":"575","author":"Li","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.scib.2024.03.056_b0600","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41467-022-28520-4","article-title":"The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system","volume":"13","author":"Ji","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.scib.2024.03.056_b0605","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41586-021-04220-9","article-title":"Synthon-based ligand discovery in virtual libraries of over 11 billion compounds","volume":"601","author":"Sadybekov","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.scib.2024.03.056_b0610","doi-asserted-by":"crossref","first-page":"6509","DOI":"10.1038\/s41467-023-42233-2","article-title":"Expanding protactable genome universe of E3 ligases","volume":"14","author":"Liu","year":"2023","journal-title":"Nat Commun"}],"container-title":["Science Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2095927324002123?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2095927324002123?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:40:44Z","timestamp":1778838044000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2095927324002123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":122,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["S2095927324002123"],"URL":"https:\/\/doi.org\/10.1016\/j.scib.2024.03.056","relation":{},"ISSN":["2095-9273"],"issn-type":[{"value":"2095-9273","type":"print"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting the undruggables\u2014the power of protein degraders","name":"articletitle","label":"Article Title"},{"value":"Science Bulletin","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.scib.2024.03.056","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Science China Press. Published by Elsevier B.V. and Science China Press.","name":"copyright","label":"Copyright"}]}}