{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:23:08Z","timestamp":1785410588728,"version":"3.56.0"},"reference-count":168,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82272599"],"award-info":[{"award-number":["82272599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82272599"],"award-info":[{"award-number":["82272599"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"crossref","award":["2024NSFSC1575"],"award-info":[{"award-number":["2024NSFSC1575"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sichuan Science and Technology Program","award":["2024NSFSC0539"],"award-info":[{"award-number":["2024NSFSC0539"]}]},{"name":"1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University","award":["ZYGD23014"],"award-info":[{"award-number":["ZYGD23014"]}]},{"award":["ZYGD23014"],"award-info":[{"award-number":["ZYGD23014"]}],"id":[{"id":"https:\/\/ror.org\/011ashp19","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Targeted Protein Degradation (TPD) has emerged as a transformative paradigm in drug discovery, offering a robust strategy to address \u201cundruggable\u201d targets. This study presents the first 25-year longitudinal scientometric analysis (2001\u20132025) of the TPD field, integrating data from 2750 publications across the Web of Science Core Collection, Scopus, and PubMed to map the global research landscape and therapeutic innovations. The results indicate that TPD research entered an explosive growth phase post-2016. China leads in publication volume (1247 papers), while the USA maintains dominance in citation impact (H-index = 80) and foundational leadership. The Chinese Academy of Sciences and Harvard University were identified as core institutions, with Craig M. Crews confirmed as a pivotal scholar. Thematic analysis reveals a systematic evolution from foundational ubiquitin-proteasome mechanisms to the clinical translation of advanced modalities, including Proteolysis-Targeting Chimeras (PROTACs), molecular glues, and non-ubiquitin-dependent platforms like LYTACs and AUTACs. Clinical viability is evidenced by the FDA approval of the agent ARV-471 for oncology. Despite this progress, critical challenges remain regarding E3 ligase expansion, molecular design optimization, and off-target toxicity. This review provides a data-driven roadmap for future TPD development, bridging the gap between academic output and real-world translational science to guide researchers, clinicians, and industry partners in navigating this dynamic therapeutic frontier.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070887","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:00:17Z","timestamp":1784548817000},"page":"887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping Scientific Landscapes and Therapeutic Innovations of Targeted Protein Degradation: A Scientometric Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Chong","family":"Li","sequence":"first","affiliation":[{"name":"Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"He","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjie","family":"Bao","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-0571","authenticated-orcid":false,"given":"Chengqi","family":"He","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Yang","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","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":"ref_2","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":"ref_3","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41580-024-00729-9","article-title":"Targeted protein degradation: From mechanisms to clinic","volume":"25","author":"Tsai","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","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":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cell.2019.11.031","article-title":"Proteolysis-targeting chimeras as therapeutics and tools for biological discovery","volume":"181","author":"Burslem","year":"2020","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1039\/D2CS00193D","article-title":"PROTACs: Past, present and future","volume":"51","author":"Li","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1021\/acs.accounts.5c00003","article-title":"Strategies for precise modulation of protein degradation","volume":"58","author":"He","year":"2025","journal-title":"Acc. Chem. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.1038\/s41467-025-63128-4","article-title":"LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation","volume":"16","author":"Nalawansha","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_9","first-page":"113","article-title":"Targeted protein degradation: Mechanisms, strategies and application, Signal Transduct","volume":"7","author":"Zhao","year":"2022","journal-title":"Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrd.2016.211","article-title":"Induced protein degradation: An emerging drug discovery paradigm","volume":"16","author":"Lai","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41571-023-00736-3","article-title":"Protein degraders enter the clinic\u2014A new approach to cancer therapy","volume":"20","author":"Chirnomas","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41586-024-07089-6","article-title":"Targeted protein degradation via intramolecular bivalent glues","volume":"627","author":"Hsia","year":"2024","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/anie.201914396","article-title":"Structure-based design of a macrocyclic PROTAC","volume":"59","author":"Testa","year":"2020","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.1073\/pnas.0307513100","article-title":"Searching for intellectual turning points: Progressive knowledge domain visualization","volume":"101","author":"Chen","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1517\/14712598.2012.674507","article-title":"Emerging trends in regenerative medicine: A scientometric analysis in CiteSpace","volume":"12","author":"Chen","year":"2012","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, C., and Song, M. (2019). Visualizing a field of research: A methodology of systematic scientometric reviews. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223994"},{"key":"ref_17","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":"ref_18","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":"ref_19","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":"ref_20","doi-asserted-by":"crossref","first-page":"120","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":"ref_21","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/15548627.2019.1688556","article-title":"ATTEC: A potential new approach to target proteinopathies","volume":"16","author":"Li","year":"2020","journal-title":"Autophagy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jhep.2020.04.001","article-title":"Lytic cell death in metabolic liver disease","volume":"73","author":"Gautheron","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_23","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":"ref_24","doi-asserted-by":"crossref","first-page":"34669","DOI":"10.1021\/jacs.4c13022","article-title":"Sonodynamic nano-LYTACs reverse tumor immunosuppressive microenvironment for cancer immunotherapy","volume":"146","author":"Xu","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1080\/15548627.2025.2498506","article-title":"Biochemical investigation of LC3\/GABARAP-ligand interaction as an important quality measure for LC3\/GABARAP-targeting small molecules: Addendum to the guidelines (4th edition)","volume":"21","author":"Schwalm","year":"2025","journal-title":"Autophagy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1016\/j.apsb.2025.02.025","article-title":"TRIM21-based degradation strategy for multimeric proteins","volume":"15","author":"Wang","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_27","first-page":"742","article-title":"RIPTACs expand anticancer target space","volume":"23","author":"Kingwell","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20240108","DOI":"10.1515\/ntrev-2024-0108","article-title":"Mapping evolution and trends of cell membrane-coated nanoparticles: A bibliometric analysis and scoping review","volume":"13","author":"Li","year":"2024","journal-title":"Nanotechnol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nchembio.2329","article-title":"Structural basis of PROTAC cooperative recognition for selective protein degradation","volume":"13","author":"Gadd","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.chembiol.2015.05.009","article-title":"Hijacking the e3 ubiquitin ligase cereblon to efficiently target BRD4","volume":"22","author":"Lu","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_31","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":"ref_32","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":"ref_33","doi-asserted-by":"crossref","first-page":"7124","DOI":"10.1073\/pnas.1521738113","article-title":"PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer","volume":"113","author":"Raina","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.chembiol.2017.09.010","article-title":"Lessons in PROTAC design from selective degradation with a promiscuous warhead","volume":"25","author":"Bondeson","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1002\/anie.201507978","article-title":"Small-molecule PROTACS: New approaches to protein degradation","volume":"55","author":"Toure","year":"2016","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.chembiol.2017.09.009","article-title":"The advantages of targeted protein degradation over inhibition: An RTK case study","volume":"25","author":"Burslem","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/anie.201507634","article-title":"Modular PROTAC design for the degradation of oncogenic BCR-ABL","volume":"55","author":"Lai","year":"2016","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_38","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":"ref_39","first-page":"64","article-title":"PROTACs: Great opportunities for academia and industry, Signal Transduct","volume":"4","author":"Sun","year":"2019","journal-title":"Target. Ther."},{"key":"ref_40","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":"ref_41","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nature16979","article-title":"Structural basis of lenalidomide-induced CK1\u03b1 degradation by the CRL4CRBN ubiquitin ligase","volume":"532","author":"Petzold","year":"2016","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41589-018-0055-y","article-title":"Plasticity in binding confers selectivity in ligand-induced protein degradation","volume":"14","author":"Nowak","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.pharmthera.2017.02.027","article-title":"Targeted protein degradation by PROTACs","volume":"174","author":"Neklesa","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_44","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":"ref_45","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1074\/mcp.T300009-MCP200","article-title":"Development of protacs to target cancer-promoting proteins for ubiquitination and degradation","volume":"2","author":"Sakamoto","year":"2003","journal-title":"Mol. Cell. Proteom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7201","DOI":"10.1038\/onc.2008.320","article-title":"Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer","volume":"27","author":"Cyrus","year":"2008","journal-title":"Oncogene"},{"key":"ref_47","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. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41589-019-0279-5","article-title":"Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16","volume":"15","author":"Zhang","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.chembiol.2020.07.020","article-title":"PROTACs: An emerging therapeutic modality in precision medicine","volume":"27","author":"Nalawansha","year":"2020","journal-title":"CELL Chem. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.chembiol.2017.10.005","article-title":"A chemoproteomic approach to query the degradable kinome using a multi-kinase degrader","volume":"25","author":"Huang","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23299","DOI":"10.1002\/anie.202107347","article-title":"Aptamer-PROTAC conjugates (APCs) for tumor-specific targeting in breast cancer","volume":"60","author":"He","year":"2021","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1021\/jacs.1c00451","article-title":"Cancer selective target degradation by folate-caged PROTACs","volume":"143","author":"Liu","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8216","DOI":"10.1039\/D2CS00387B","article-title":"Discovery of small molecule ligands for the von hippel-lindau (VHL) e3 ligase and their use as inhibitors and PROTAC degraders","volume":"51","author":"Diehl","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1021\/acs.jmedchem.7b00675","article-title":"Group-based optimization of potent and cell-active inhibitors of the von hippel-lindau (VHL) e3 ubiquitin ligase: Structure-activity relationships leading to the chemical probe (2s,4r)-1-((s)-2-(1-cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyi)-4-hydroxy-n-(4-(4-methylthiazol-5-yl)benzypp yrrolidine-2-carboxamide (VH298)","volume":"61","author":"Soares","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5498","DOI":"10.1039\/D2CS00197G","article-title":"Chasing molecular glue degraders: Screening approaches","volume":"51","author":"Domostegui","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1021\/acs.jmedchem.8b01631","article-title":"Discovery of ARD-69 as a highly potent proteolysis targeting chimera (PROTAC) degrader of androgen receptor (AR) for the treatment of prostate cancer","volume":"62","author":"Han","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_57","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":"ref_58","doi-asserted-by":"crossref","first-page":"e202114957","DOI":"10.1002\/anie.202114957","article-title":"Smart nano-PROTACs reprogram tumor microenvironment for activatable photo-metabolic cancer immunotherapy","volume":"61","author":"Zhang","year":"2022","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2202039","DOI":"10.1002\/advs.202202039","article-title":"Versatile nano-PROTAC-induced epigenetic reader degradation for efficient lung cancer therapy","volume":"9","author":"Zhang","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2314132","DOI":"10.1002\/adma.202314132","article-title":"PROTAC prodrug-integrated nanosensitizer for potentiating radiation therapy of cancer","volume":"36","author":"Zhang","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1021\/acschembio.5b00442","article-title":"HaloPROTACS: Use of small molecule PROTACs to induce degradation of halo tag fusion proteins","volume":"10","author":"Buckley","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_62","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":"ref_63","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1021\/acs.biochem.8b00391","article-title":"Targeting the c481s ibrutinib-resistance mutation in bruton\u2019s tyrosine kinase using PROTAC-mediated degradation","volume":"57","author":"Buhimschi","year":"2018","journal-title":"Biochemistry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5683","DOI":"10.1021\/acs.jmedchem.3c02332","article-title":"Beyond rule of five and PROTACs in modern drug discovery: Polarity reducers, chameleonicity, and the evolving physicochemical landscape","volume":"67","author":"Price","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"103917","DOI":"10.1016\/j.drudis.2024.103917","article-title":"Exploring the chemical space of orally bioavailable PROTACs","volume":"29","author":"Apprato","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"13106","DOI":"10.1021\/acs.jmedchem.4c01017","article-title":"Structural and physicochemical features of oral PROTACs","volume":"67","author":"Schade","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_67","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":"ref_68","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.1039\/C7CC03879H","article-title":"Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC)","volume":"53","author":"Robb","year":"2017","journal-title":"Chem. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-pharmtox-010715-103507","article-title":"Targeted protein degradation by small molecules","volume":"57","author":"Bondeson","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"115447","DOI":"10.1016\/j.ejmech.2023.115447","article-title":"Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications","volume":"257","author":"Li","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10549-024-07403-w","article-title":"BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436","volume":"208","author":"Teufelsbauer","year":"2024","journal-title":"Breast. Cancer. Res. Treat."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1038\/s41401-024-01312-w","article-title":"A novel FAK-degrading PROTAC molecule exhibited both anti-tumor activities and efficient MDR reversal effects","volume":"45","author":"Xu","year":"2024","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13029","DOI":"10.1021\/acs.jmedchem.2c00877","article-title":"Linker-dependent folding rationalizes PROTAC cell permeability","volume":"65","author":"Poongavanam","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12639","DOI":"10.1021\/acs.jmedchem.2c00201","article-title":"Designing soluble PROTACs: Strategies and preliminary guidelines","volume":"65","author":"Jimenez","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1021\/acsmedchemlett.4c00189","article-title":"Interplay of PROTAC complex dynamics for undruggable targets: Insights into ternary complex behavior and linker design","volume":"15","author":"Kumar","year":"2024","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"102783","DOI":"10.1016\/j.redox.2023.102783","article-title":"Development of KEAP1-targeting PROTAC and its antioxidant properties: In vitro and in vivo","volume":"64","author":"Park","year":"2023","journal-title":"Redox Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"102552","DOI":"10.1016\/j.redox.2022.102552","article-title":"Design and characterization of a heterobifunctional degrader of KEAP1","volume":"59","author":"Chen","year":"2023","journal-title":"Redox Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1021\/acs.jmedchem.2c01909","article-title":"Are-PROTACs enable co-degradation of an nrf2-MafG heterodimer","volume":"66","author":"Ji","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"D1683","DOI":"10.1093\/nar\/gkaf996","article-title":"TPDdb: The comprehensive database of targeted protein degrader","volume":"54","author":"Qin","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1038\/s41597-025-06136-9","article-title":"PROTAC-PatentDB: A PROTAC patent compound dataset","volume":"12","author":"Cai","year":"2025","journal-title":"Sci. Data"},{"key":"ref_81","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":"ref_82","doi-asserted-by":"crossref","first-page":"D1367","DOI":"10.1093\/nar\/gkac946","article-title":"PROTAC-DB 2.0: An updated database of PROTACs","volume":"51","author":"Weng","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"D1510","DOI":"10.1093\/nar\/gkae768","article-title":"PROTAC-DB 3.0: An updated database of PROTACs with extended pharmacokinetic parameters","volume":"53","author":"Ge","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bai, F., Tian, S., Tang, Y., Li, F., and Li, Z. (2024). PROTAC-databank: The present largest integrated resource of PROTACs, enabling the enhanced DeepPROTACs 2.0 for degradation prediction. Res. Sq.","DOI":"10.21203\/rs.3.rs-5021266\/v1"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/cbdd.14123","article-title":"ELIOT: A platform to navigate the e3 pocketome and aid the design of new PROTACs","volume":"101","author":"Palomba","year":"2023","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"D593","DOI":"10.1093\/nar\/gkac860","article-title":"MeDBA: The metalloenzyme data bank and analysis platform","volume":"51","author":"Yu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"D1510","DOI":"10.1093\/nar\/gkaf811","article-title":"MolGlueDB: An online database of molecular glues","volume":"54","author":"Wang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"baae111","DOI":"10.1093\/database\/baae111","article-title":"ELiAH: The atlas of e3 ligases in human tissues for targeted protein degradation with reduced off-target effect","volume":"2024","author":"Paik","year":"2024","journal-title":"Database"},{"key":"ref_89","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."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"baab010","DOI":"10.1093\/database\/baab010","article-title":"UbiNet 2.0: A verified, classified, annotated and updated database of e3 ubiquitin ligase-substrate interactions","volume":"2021","author":"Li","year":"2021","journal-title":"Database"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1093\/bioinformatics\/bty1067","article-title":"UbiHub: A data hub for the explorers of ubiquitination pathways","volume":"35","author":"Liu","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9541","DOI":"10.1021\/acs.jcim.5c00880","article-title":"Data-driven generation of conformational ensembles and ternary complexes for PROTAC and other chimera systems","volume":"65","author":"Montisci","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1038\/s41598-024-83558-2","article-title":"MEGA PROTAC, MEGA DOCK-based PROTAC mediated ternary complex formation pipeline with sequential filtering and rank aggregation","volume":"15","author":"Ugurlu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1021\/acs.jcim.3c01878","article-title":"PROTACable is an integrative computational pipeline of 3-d modeling and deep learning to automate the de novo design of PROTACs","volume":"64","author":"Mslati","year":"2024","journal-title":"J. Chem. Inf. Model."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6823","DOI":"10.1021\/acs.jcim.3c01154","article-title":"Rational prediction of PROTAC-compatible protein-protein interfaces by molecular docking","volume":"63","author":"Pereira","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"16271","DOI":"10.1021\/acs.jmedchem.1c01576","article-title":"Integrative modeling of PROTAC-mediated ternary complexes","volume":"64","author":"Weng","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4894","DOI":"10.1021\/acs.jcim.0c00589","article-title":"PRosettaC: Rosetta based modeling of PROTAC mediated ternary complexes","volume":"60","author":"Zaidman","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_98","unstructured":"(2025, July 03). A Phase II, Randomized, Open-Label, Multi-Center Study of JSB462 (Luxdegalutamide) in Combination with Lutetium (177lu) Vipivotide Tetraxetan in Adult Male Patients with PSMA-Positive Metastatic Castration Resistant Prostate Cancer (mCRPC), Available online: https:\/\/clinicaltrials.gov\/study\/NCT07047118."},{"key":"ref_99","unstructured":"(2019, March 01). A Phase 1\/2, Open-Label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-110 in Patients with Metastatic Castration Resistant Prostate Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03888612."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.annonc.2024.09.005","article-title":"Safety and clinical activity of bms-986365, a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer","volume":"36","author":"Rathkopf","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_101","unstructured":"(2023, February 22). A Phase i Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of AC176 in Chinese Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05673109."},{"key":"ref_102","unstructured":"(2023, December 26). A Phase i\/II Open-Label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral HP518 in Patients with Metastatic Castration-Resistant Prostate Cancer in China, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06155084."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10637-025-01533-8","article-title":"Phase 1 study of HP518, a PROTAC AR degrader in patients with mCRPC: Results on safety, pharmacokinetics, and anti-tumor activity","volume":"43","author":"Azad","year":"2025","journal-title":"Investig. New. Drugs"},{"key":"ref_104","unstructured":"(2020, June 22). A Phase 1, Multi-Center, Open-Label, Dose Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of cc-94676 in Subjects with Metastatic Castration-Resistant Prostate Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04428788."},{"key":"ref_105","unstructured":"(2023, August 31). Tolerance, Safety, Pharmacokinetics, and Preliminary Anti-Tumor Activity of QLH12016 in Patients with Metastatic Castration Resistant Prostate Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05973149."},{"key":"ref_106","unstructured":"(2023, August 03). A Phase i Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of HRS-5041 in Subjects with Metastatic Castration-Resistant Prostate Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05942001."},{"key":"ref_107","unstructured":"(2025, March 24). A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose Escalation Study in Subjects to Evaluate the Safety, Tolerability and Pharmacokinetics of AH-001 Following Topical Single and Multiple Ascending Dose Administration, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06927960."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"LBA1000","DOI":"10.1200\/JCO.2025.43.17_suppl.LBA1000","article-title":"Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive\/human epidermal growth factor receptor 2 (HER2)\u2013negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study","volume":"43","author":"Hamilton","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Hamilton, E.P., De Laurentiis, M., Jhaveri, K., Hu, X., Ladoire, S., Patsouris, A., Zamagni, C., Cui, J., Cazzaniga, M., and Cil, T. (2026). Abstract PD10-03: Subgroup analyses of VERITAC-2: A phase 3 trial of vepdegestrant, a PROTAC estrogen receptor (ER) degrader, versus fulvestrant in ER-positive\/ human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (aBC). Clin. Cancer Res., 32.","DOI":"10.1158\/1557-3265.SABCS25-PD10-03"},{"key":"ref_110","unstructured":"(2025, January 07). A Multicenter, Open, Dose Escalation\/Dose Escalation, and Phase i\/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral HP568 Tablets Alone and in Combination with Palbociclib in Patients with ER+\/HER2 Advanced Breast Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06757335."},{"key":"ref_111","unstructured":"(2022, October 01). A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of AC682 in Chinese Patients with ER+\/HER2\u2212 Locally Advanced or Metastatic Breast Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05489679."},{"key":"ref_112","unstructured":"(2023, February 07). A Single-Arm, Open-Label, Multi-Center Phase i Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HRS-1358 Monotherapy or Combination with Dalpiciclib Isethionate Tablets in Patients with Metastatic or Locally Advanced Breast Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05628870."},{"key":"ref_113","unstructured":"(2025, April 10). A Phase 3, Open-Label, Randomized Study of BGB-16673 Compared to Investigator\u2019s Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab or Venetoclax Plus Rituximab Retreatment) in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to both BTK and BCL2 Inhibitors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06846671."},{"key":"ref_114","unstructured":"(2021, May 05). A Phase 1, Dose Escalation, Safety and Tolerability Study of NX-2127, a Bruton\u2019s Tyrosine Kinase (BTK) Degrader, in Adults with Relapsed\/Refractory b-Cell Malignancies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04830137."},{"key":"ref_115","unstructured":"(2022, April 13). A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton\u2019s Tyrosine Kinase (BTK) Degrader, in Adults with Relapsed\/Refractory b-Cell Malignancies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05131022."},{"key":"ref_116","unstructured":"(2023, June 20). A Phase ia\/b Clinical Study on Safety, Tolerability, and Pharmacokinetics\/Pharmacodynamics of BTK Protein Degradation Agent HSK29116 in Subjects with Relapsed or Refractory b-Cell Malignancy, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04861779."},{"key":"ref_117","unstructured":"(2021, August 24). A Phase i Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TQB3019 Capsules in Subjects with Advanced Malignant Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06943677."},{"key":"ref_118","unstructured":"(2023, June 20). A Phase I Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Malignancy Activity of AC676 in Patients with Relapsed\/Refractory b-Cell Malignancies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05780034."},{"key":"ref_119","unstructured":"(2022, March 25). A Phase 1\/2 Open-Label, Multicenter Study to Characterize the Safety and Tolerability of CFT8634 in Subjects with Locally Advanced or Metastatic Smarcb1-Perturbed Cancers, Including Synovial Sarcoma and Smarcb1-Null Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05355753."},{"key":"ref_120","unstructured":"(2021, August 17). A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered FHD-609 in Subjects with Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04965753."},{"key":"ref_121","unstructured":"(2025, April 15). A Phase I\/II, Dose-Escalation and Dose-Optimization Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of MT-4561 in Patients with Various Advanced Solid Tumors and to Evaluate Effect of MT-4561 on Pharmacokinetics of Oral Midazolam, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06932003."},{"key":"ref_122","unstructured":"(2025, April 22). A Phase ic\/II Clinical Study to Explore the Safety, Tolerability, Efficacy, and Pharmacokinetics of Multiple Oral Doses of LT-002-158 Tablets in Chinese Adult Patients with Hidradenitis Suppurativa. Available online: https:\/\/adisinsight.springer.com\/trials\/700382079."},{"key":"ref_123","unstructured":"(2021, February 23). A Phase 1 Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered KT-474 in Healthy Adult Volunteers and Patients with Atopic Dermatitis (AD) or Hidradenitis Suppurativa (HS), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04772885."},{"key":"ref_124","unstructured":"(2022, June 13). A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, PK\/PD, and Clinical Activity of Intravenously Administered KT-413 in Adult Patients with Relapsed or Refractory b-cell NHL, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05233033."},{"key":"ref_125","unstructured":"(2024, June 20). Phase 1a\/1b Randomized Study to Evaluate the safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single- and Multiple-Ascending Doses and Food Effect of BGB-45035 in Healthy Participants and Its Safety and Tolerability in Patients with Autoimmune Dermatological Diseases, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06342713."},{"key":"ref_126","unstructured":"(2024, December 13). A Phase i Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of CFT8919 Capsules in Patients with Locally Advanced or Metastatic Non-Small Cell LUNG Cancer (NSCLC), Available online: https:\/\/clinicaltrials.gov\/study\/NCT06641609."},{"key":"ref_127","unstructured":"(2023, March 27). A Phase i, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of HSK40118 in Patients with EGFR Mutation Locally Advanced or Metastatic NSCLC, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06050980."},{"key":"ref_128","unstructured":"(2024, December 05). Phase 1a\/1b, Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of a CDAC Degrading EGFR, BG-60366, in Patients with EGFR-Mutant Non-Small Cell Lung Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06685718."},{"key":"ref_129","unstructured":"(2023, December 29). A Phase 1\/2, Multi-Center, Open-Label, Dose-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BMS-986458, Alone and in Combination with Anti-Lymphoma Agents in Participants with Relapsed\/Refractory Non-Hodgkin Lymphomas (r\/r NHL), Available online: https:\/\/clinicaltrials.gov\/study\/NCT06090539."},{"key":"ref_130","unstructured":"(2024, September 05). A Phase 1 First in Human Study of ARV-393 in Adult Participants with Advanced Non-Hodgkin\u2019s Lymphoma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06393738."},{"key":"ref_131","unstructured":"(2022, June 08). A Phase 1 Study of ASP3082 in Participants with Locally Advanced or Metastatic Solid Tumor Malignancies with KRAS g12d Mutation, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05382559."},{"key":"ref_132","unstructured":"(2024, December 19). A Phase 1, Open-Label Dose Escalation and Expansion Study of PT0253 in Participants with KRAS g12d Mutated Advanced Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06797336."},{"key":"ref_133","unstructured":"(2024, April 16). An Open-Label Phase 1 Study of ASP4396 in Participants with Locally Advanced (Unresectable) or Metastatic Solid Tumor Malignancies with KRAS g12d Mutation, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06364696."},{"key":"ref_134","unstructured":"(2025, June 12). DT2216 in Combination with Irinotecan for Children, Adolescents and Young Adults with Relapsed or Refractory Solid Tumors: A Phase i Study with Phase II Feasibility Cohort for Fibrolamellar Carcinoma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06620302."},{"key":"ref_135","unstructured":"(2022, May 19). A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered KT-333 in Adult Patients with Relapsed or Refractory Lymphomas, Large Granular Lymphocytic Leukemia, and Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05225584."},{"key":"ref_136","unstructured":"(2022, December 08). A Phase 1\/2 Open-Label Multicenter Trial to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and Combination Therapy in Subjects with BRAF v600 Mutant Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05668585."},{"key":"ref_137","unstructured":"(2025, June 03). A Phase 2, Safety and Efficacy Study of PRT3789 in Combination with Pembrolizumab in Patients with Advanced or Metastatic Solid Tumors with a SMARCA4 Mutation, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06682806."},{"key":"ref_138","unstructured":"(2025, June 12). A Phase 1\/2a, First-in-Human, Randomized, Double-Blinded, Placebo-Controlled, Dose-Finding Study in Healthy Volunteers and Participants with Sickle Cell Disease to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, ph and Food Effect, and Preliminary Efficacy of BMS-986470, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06481306."},{"key":"ref_139","unstructured":"(2024, July 17). A Phase 1 Study of AUTX-703 in Participants with Relapsed\/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndromes, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06846606."},{"key":"ref_140","unstructured":"(2025, November 24). A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Dose-Ranging Study with an Open-Label Period Investigating the Efficacy and Safety Profile of KT-621 Administered Orally to Participants with Moderate to Severe Atopic Dermatitis, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07217015."},{"key":"ref_141","unstructured":"(2023, May 15). A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered KT-253 in Adult Patients with High Grade Myeloid Malignancies and Acute Lymphocytic Leukemia, Lymphoma, and Advanced Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05775406."},{"key":"ref_142","unstructured":"(2023, August 11). An Open-Label, Multicenter, Phase i Study of AXT-1003 as a Single Agent in Adult Subjects with Relapsed\/Refractory Non-hodgkin Lymphomas, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05965505."},{"key":"ref_143","unstructured":"(2024, September 19). A Phase 1, First-in-Human, Open-Label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-Tumor Activity of the Novel Oral CDK2 Degrader NKT3964 in Adults with Advanced\/Metastatic Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06586957."},{"key":"ref_144","unstructured":"(2024, July 03). A First-in-Human, Open-Label, Dose Escalation and Expansion Trial of BTX-9341 in Participants with Advanced and\/or Metastatic Breast Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06515470."},{"key":"ref_145","unstructured":"(2024, March 15). Phase 2 Trial of Obinutuzumab and CC-99282 for Patients with Previously Untreated High Tumor Burden Follicular Lymphoma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06108232."},{"key":"ref_146","unstructured":"(2023, February 06). A Multicenter Phase 1-DEC (Dose Expansion Cohort) Open-Label Study of Iberdomide (CC-220) in Combination with Elotuzumab and Dexamethasone for Relapsed\/Refractory Multiple Myeloma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05560399."},{"key":"ref_147","unstructured":"(2014, September 16). A Pilot, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Study to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of CC-220 in Subjects with Systemic Lupus Erythematosus, Available online: https:\/\/clinicaltrials.gov\/study\/NCT02185040."},{"key":"ref_148","unstructured":"(2014, November 01). A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Sequential, Dose-Ascending Study of CC-220 in Subjects with Chronic Cutaneous Sarcoidosis, Available online: https:\/\/clinicaltrials.gov\/study\/NCT02192489."},{"key":"ref_149","unstructured":"(2018, February 06). A Phase 1\/2 Multicenter, Open-Label Study to Assess the Safety, Pharmacokinetics and Efficacy of CC-92480 Monotherapy and in Combination with Dexamethasone in Subjects with Relapsed and Refractory Multiple Myeloma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03374085."},{"key":"ref_150","unstructured":"(2021, June 03). A Phase 1b\/2a Multicenter Study to Assess the Safety and Tolerability, Pharmacokinetics, and Preliminary Efficacy of KPG-818 in Patients with Systemic Lupus Erythematosus, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04643067."},{"key":"ref_151","unstructured":"(2011, September 12). A Phase 1a\/1b, Multi-Center, Open-Label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Pleiotropic Pathway Modifier CC-122 Administered Orally to Subjects with Advanced Solid Tumors, Non-Hodgkin\u2019s Lymphoma, or Multiple Myeloma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT01421524."},{"key":"ref_152","unstructured":"(2021, April 27). A Phase 1\/2 Open-Label Multi-Center Study to Characterize the Safety and Tolerability of CFT7455 in Subjects with Relapsed\/Refractory Non-Hodgkin\u2019s LYMPHOMA or Multiple Myeloma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04756726."},{"key":"ref_153","unstructured":"(2022, January 24). An Open Label, Escalating Multiple Dose Study to Evaluate the Safety, Toxicity, Pharmacokinetics, and Preliminary Activity of BTX-1188 in Subjects with Advanced Malignancies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05144334."},{"key":"ref_154","unstructured":"(2019, November 26). A First-in-Human Study to Determine the Safety, Pharmacokinetics and Efficacy of KPG-121 When Administered with Enzalutamide, Abiraterone, or Apalutamide in Subjects with Non-Metastatic or Metastatic Castration-Resistant Prostate Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03569280."},{"key":"ref_155","unstructured":"(2019, May 07). A Phase i\/ib, Open-Label, Multi-Center, Study of DKY709 as a Single Agent and in Combination with PDR001 in Patients with Advanced Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03891953."},{"key":"ref_156","unstructured":"(2021, August 31). A Phase i Study to Evaluate the Tolerability and Pharmacokinetics of TQB3820 in Relapsed or Refractory Multiple Myeloma (r\/r MM) or Relapsed or Refractory Indolent b-Cell Non-Hodgkin\u2019s Lymphoma (r\/r b-NHL), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05020639."},{"key":"ref_157","unstructured":"(2022, October 12). A Phase 1\/2 Study of Oral MRT-2359 in Patients with MYC-Driven and Other Selected Solid Tumors Including Lung Cancer and Diffuse b-Cell Lymphoma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05546268."},{"key":"ref_158","unstructured":"(2020, August 05). An Exploratory Phase 1b Open-Label Multi-Arm Trial to Evaluate the Safety and Efficacy of CC-90009 in Combination with Anti-Leukemia Agents in Subjects with Acute Myeloid Leukemia, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04336982."},{"key":"ref_159","unstructured":"(2007, September 24). A Single Arm Phase II Study of the Efficacy, Safety, and Biomarkers of Activity of e7820 Plus Cetuximab in Advanced Solid Tumors Preceded by a Run-in Study to Determine Safety of the Combination, Available online: https:\/\/clinicaltrials.gov\/study\/NCT00309179."},{"key":"ref_160","unstructured":"(2023, March 29). A Multi-Center, Non-Randomized, and Open-Label Phase I\/IIa Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of ICP-490 in Patients with Relapsed and\/or Refractory Multiple Myeloma, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05719701."},{"key":"ref_161","unstructured":"(2022, January 30). A Phase i Trial of ATG-101 in Patients with Metastatic\/Advanced Solid Tumors and Mature b-Cell Non-Hodgkin Lymphomas, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05490043."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"118427","DOI":"10.1016\/j.bmc.2025.118427","article-title":"Synthesis and degradation effect of PROTACs targeting EGFR triple mutants","volume":"132","author":"Xi","year":"2026","journal-title":"Bioorg. Med. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"118199","DOI":"10.1016\/j.ejmech.2025.118199","article-title":"Highly potent and selective degrader targeting ER\u03b1 to improve the treatment outcomes of breast cancer","volume":"301","author":"Bao","year":"2026","journal-title":"Eur. J. Med. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"254","DOI":"10.7150\/thno.114005","article-title":"Clathrin mediated endocytosis targeting chimera for targeted membrane proteins degradation and enhance CAR-t cell anti-tumor therapy","volume":"16","author":"Li","year":"2026","journal-title":"Theranostics"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"118208","DOI":"10.1016\/j.ejmech.2025.118208","article-title":"Antiviral strategies based on targeted protein degradation: An overview of the literature and future outlook","volume":"301","author":"Zhou","year":"2026","journal-title":"Eur. J. Med. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"130428","DOI":"10.1016\/j.bmcl.2025.130428","article-title":"Design and validation of the first-in-class PROTACs for targeted degradation of the immune checkpoint LAG-3","volume":"130","author":"Vazquez","year":"2026","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"118202","DOI":"10.1016\/j.ejmech.2025.118202","article-title":"Mighty mini-PROTACs: An emerging class of degraders","volume":"301","author":"Chen","year":"2026","journal-title":"Eur. J. Med. Chem."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"118253","DOI":"10.1016\/j.ejmech.2025.118253","article-title":"A double-edged sword of neo-substrate degradation in PROTACs","volume":"301","author":"Song","year":"2026","journal-title":"Eur. J. Med. Chem."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:23:42Z","timestamp":1784694222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":168,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pharmaceutics18070887"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18070887","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}