{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:36:23Z","timestamp":1792859783443,"version":"4.5.0"},"reference-count":78,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFA0922400"],"award-info":[{"award-number":["2025YFA0922400"]}],"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":["82304291"],"award-info":[{"award-number":["82304291"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017415","name":"Peking University First Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020732","name":"Innovative Research Team of High-level Local Universities in Shanghai","doi-asserted-by":"publisher","award":["2025YC29"],"award-info":[{"award-number":["2025YC29"]}],"id":[{"id":"10.13039\/100020732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Discovery Today"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.drudis.2026.104820","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:51:21Z","timestamp":1791215481000},"page":"104820","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting IKZF2 with molecular glue degraders for cancer immunotherapy"],"prefix":"10.1016","volume":"31","author":[{"given":"Yaoguang","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoqi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7509-2157","authenticated-orcid":false,"given":"Wenwu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.drudis.2026.104820_b0005","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N Engl J Med"},{"key":"10.1016\/j.drudis.2026.104820_b0010","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N Engl J Med"},{"key":"10.1016\/j.drudis.2026.104820_b0015","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.drudis.2026.104820_b0020","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41571-019-0175-7","article-title":"Regulatory T cells in cancer immunosuppression \u2014 implications for anticancer therapy","volume":"16","author":"Togashi","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1016\/j.drudis.2026.104820_b0025","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat Med"},{"key":"10.1016\/j.drudis.2026.104820_b0030","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nm1093","article-title":"Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival","volume":"10","author":"Curiel","year":"2004","journal-title":"Nat Med"},{"key":"10.1016\/j.drudis.2026.104820_b0035","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2026.104820_b0040","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nri2343","article-title":"How regulatory T cells work","volume":"8","author":"Vignali","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0045","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/cr.2016.151","article-title":"Regulatory T cells in cancer immunotherapy","volume":"27","author":"Tanaka","year":"2017","journal-title":"Cell Res"},{"key":"10.1016\/j.drudis.2026.104820_b0050","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccell.2023.02.014","article-title":"Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy","volume":"41","author":"Tay","year":"2023","journal-title":"Cancer Cell"},{"key":"10.1016\/j.drudis.2026.104820_b0055","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1101\/gad.12.6.782","article-title":"Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin","volume":"12","author":"Hahm","year":"1998","journal-title":"Genes Dev"},{"key":"10.1016\/j.drudis.2026.104820_b0060","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.4049\/jimmunol.0904028","article-title":"Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells","volume":"184","author":"Thornton","year":"2010","journal-title":"J Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0065","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0024226","article-title":"Helios expression is a marker of T cell activation and proliferation","volume":"6","author":"Akimova","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.drudis.2026.104820_b0070","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.4049\/jimmunol.1201379","article-title":"Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans","volume":"190","author":"Himmel","year":"2013","journal-title":"J Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0075","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1126\/science.aad0616","article-title":"Stable inhibitory activity of regulatory T cells requires the transcription factor Helios","volume":"350","author":"Kim","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.drudis.2026.104820_b0080","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1073\/pnas.1604765113","article-title":"Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity","volume":"113","author":"Nakagawa","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2026.104820_b0085","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41589-021-00802-w","article-title":"Acute pharmacological degradation of Helios destabilizes regulatory T cells","volume":"17","author":"Wang","year":"2021","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.drudis.2026.104820_b0090","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.chembiol.2023.02.005","article-title":"Discovery and characterization of a selective IKZF2 glue degrader for cancer immunotherapy","volume":"30","author":"Bonazzi","year":"2023","journal-title":"Cell Chem Biol"},{"key":"10.1016\/j.drudis.2026.104820_b0095","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1182\/bloodadvances.2021006367","article-title":"Identification of germline monoallelic mutations in IKZF2 in patients with immune dysregulation","volume":"6","author":"Shahin","year":"2022","journal-title":"Blood Adv"},{"key":"10.1016\/j.drudis.2026.104820_b0100","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1136\/jmg-2022-109127","article-title":"Dominant negative variants in IKZF2 cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay","volume":"60","author":"Mohajeri","year":"2023","journal-title":"J Med Genet"},{"key":"10.1016\/j.drudis.2026.104820_b0105","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10875-025-01882-2","article-title":"A germline heterozygous dominant negative IKZF2 variant causing syndromic primary immune regulatory disorder and ICHAD","volume":"45","author":"Lu","year":"2025","journal-title":"J Clin Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0110","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.drudis.2026.104820_b0115","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.drudis.2026.104820_b0120","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.drudis.2026.104820_b0125","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nsmb.2874","article-title":"Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs","volume":"21","author":"Chamberlain","year":"2014","journal-title":"Nat Struct Mol Biol"},{"key":"10.1016\/j.drudis.2026.104820_b0130","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.drudis.2026.104820_b0135","doi-asserted-by":"crossref","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.drudis.2026.104820_b0140","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nature14610","article-title":"Lenalidomide induces ubiquitination and degradation of CK1\u03b1 in del(5q) MDS","volume":"523","author":"Kr\u00f6nke","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2026.104820_b0145","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/s41589-018-0129-x","article-title":"SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate","volume":"14","author":"Matyskiela","year":"2018","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.drudis.2026.104820_b0150","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1038\/s41467-025-58431-z","article-title":"Development of PVTX-405 as a potent and highly selective molecular glue degrader of IKZF2 for cancer immunotherapy","volume":"16","author":"Chen","year":"2025","journal-title":"Nat Commun"},{"key":"10.1016\/j.drudis.2026.104820_b0155","doi-asserted-by":"crossref","first-page":"16953","DOI":"10.1021\/acs.jmedchem.3c01736","article-title":"Design and development of IKZF2 and CK1\u03b1 dual degraders","volume":"66","author":"Miyamoto","year":"2023","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2026.104820_b0160","doi-asserted-by":"crossref","first-page":"D368","DOI":"10.1093\/nar\/gkad1011","article-title":"AlphaFold Protein Structure Database in 2024: providing structure coverage for over 214 million protein sequences","volume":"52","author":"Varadi","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.drudis.2026.104820_b0165","doi-asserted-by":"crossref","unstructured":"Galli P, et al. Proteome-wide identification of the druggable CRBN interactome. Nat Biotechnol. 2026. Published online August 13, 2026. https:\/\/doi.org\/10.1038\/s41587-026-03237-7.","DOI":"10.1038\/s41587-026-03237-7"},{"key":"10.1016\/j.drudis.2026.104820_b0170","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nature13527","article-title":"Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide","volume":"512","author":"Fischer","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2026.104820_b0175","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.drudis.2026.104820_b0180","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/s41589-020-0594-x","article-title":"Rational discovery of molecular glue degraders via scalable chemical profiling","volume":"16","author":"Mayor-Ruiz","year":"2020","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.drudis.2026.104820_b0185","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1308539","article-title":"HELIOS-expressing human CD8 T cells exhibit limited effector functions","volume":"14","author":"Neyens","year":"2023","journal-title":"Front Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0190","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.116680","article-title":"The transcription factor Helios restrains the anti-tumor capacity of CD8+ T cells","volume":"44","author":"Rubio","year":"2025","journal-title":"Cell Rep"},{"key":"10.1016\/j.drudis.2026.104820_b0195","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41586-018-0728-4","article-title":"Helios is a key transcriptional regulator of outer hair cell maturation","volume":"563","author":"Chessum","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2026.104820_b0200","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abe3454","article-title":"Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells","volume":"6","author":"Hetem\u00e4ki","year":"2021","journal-title":"Sci Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0205","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20202317","article-title":"Helios represses megakaryocyte priming in hematopoietic stem and progenitor cells","volume":"218","author":"Cova","year":"2021","journal-title":"J Exp Med"},{"key":"10.1016\/j.drudis.2026.104820_b0210","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1002\/eji.201848075","article-title":"Suppression of Aiolos and Ikaros expression by lenalidomide reduces human ILC3-ILC1\/NK cell transdifferentiation","volume":"49","author":"Mazzurana","year":"2019","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0215","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.4049\/jimmunol.1200792","article-title":"Helios induces epigenetic silencing of Il2 gene expression in regulatory T cells","volume":"190","author":"Baine","year":"2013","journal-title":"J Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0220","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4049\/jimmunol.1501704","article-title":"Helios controls a limited subset of regulatory T cell functions","volume":"196","author":"Sebastian","year":"2016","journal-title":"J Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0225","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/eji.202149318","article-title":"Helios is a marker, not a driver, of human Treg stability","volume":"52","author":"Lam","year":"2022","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0230","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1073\/pnas.1720447115","article-title":"Comparative transcriptome analysis reveals distinct genetic modules associated with Helios expression in intratumoral regulatory T cells","volume":"115","author":"Yates","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2026.104820_b0235","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.cell.2017.05.005","article-title":"Interferon-\u03b3 drives Treg fragility to promote anti-tumor immunity","volume":"169","author":"Overacre-Delgoffe","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2026.104820_b0240","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41590-018-0051-0","article-title":"Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR","volume":"19","author":"Zemmour","year":"2018","journal-title":"Nat Immunol"},{"key":"10.1016\/j.drudis.2026.104820_b0245","unstructured":"Australian New Zealand Clinical Trials Registry. A Phase 1, Randomized, Placebo-Controlled Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of PLX-4545 in Healthy Subjects. ACTRN12623001265662. https:\/\/anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?ACTRN=12623001265662 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0250","unstructured":"Thompson P, et al. A First-in-Human Study of PLX-4545, a Molecular Glue Degrader of IKZF2, in Healthy Volunteers, Shows Pharmacologic Modulation of Tregs at Well-Tolerated Doses [poster]. AACR Annual Meeting. 2025. https:\/\/plexium.com\/wp-content\/uploads\/2025\/04\/2025-aacr-a-first-in-human-study-of-plx-4545-a-molecular-glue-degrader-of-ikzf2-in-healthy-volunteers.pdf [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0255","unstructured":"ClinicalTrials.gov. Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors. NCT03891953. https:\/\/clinicaltrials.gov\/study\/NCT03891953 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0260","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.drudis.2026.104820_b0265","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":"10.1016\/j.drudis.2026.104820_b0270","unstructured":"ClinicalTrials.gov. A Study of BTX-A51 in People With Advanced Solid Tumor and Breast Cancer. NCT04872166. https:\/\/clinicaltrials.gov\/study\/NCT04872166 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0275","unstructured":"Korea National Enterprise for Clinical Trials. First-in-Human Phase 1 Dose-Escalation and Dose-Expansion Study of the CK1\u03b1-Selective Molecular Glue Degrader PIN-5018 in Advanced, Locally Advanced or Metastatic Solid Tumours. https:\/\/trialforme.konect.or.kr\/clnctest\/view.do?clncTestSn=202500581 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0280","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1021\/acschembio.2c00439","article-title":"Redirecting the neo-substrate specificity of cereblon-targeting PROTACs to Helios","volume":"17","author":"Verano","year":"2022","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.drudis.2026.104820_b0285","doi-asserted-by":"crossref","first-page":"18230","DOI":"10.1021\/acs.jmedchem.5c00668","article-title":"Discovery of a novel series of iso-indolinone-based glutarimides as highly efficacious and selective IKZF2 molecular glue degraders","volume":"68","author":"Zhang","year":"2025","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2026.104820_b0290","unstructured":"Plexium. Discovery of PLX-4545, a Molecular Glue Degrader of IKZF2. ACS Fall First-Time Disclosures. https:\/\/acs.digitellinc.com\/p\/s\/discovery-of-plx-4545-a-molecular-glue-degrader-of-ikzf2-605250 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0295","unstructured":"IUPHAR\/BPS Guide to Pharmacology. PLX-4545 ligand page. www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=13574 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0300","doi-asserted-by":"crossref","DOI":"10.1158\/1538-7445.AM2026-CT006","article-title":"Phase 1 DKY709A12101C study in patients with advanced solid tumors treated with DKY709, an IKZF2 degrader, alone or in combination with PDR001, a PD-1 inhibitor","volume":"86","author":"Garralda","year":"2026","journal-title":"Cancer Res"},{"key":"10.1016\/j.drudis.2026.104820_b0305","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2025.130263","article-title":"Overcoming CK1\u03b1 liability in the discovery of a series of isoIndolinone Glutarimides as selective IKZF2 molecular glue degraders","volume":"124","author":"Zhang","year":"2025","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.drudis.2026.104820_b0310","doi-asserted-by":"crossref","first-page":"ND05","DOI":"10.1158\/1538-7445.AM2025-ND05","article-title":"The discovery of BMS-986449, a highly potent and selective degrader of the transcription factors Helios (IKZF2) and Eos (IKZF4) for the treatment of solid tumors","volume":"85","author":"Balog","year":"2025","journal-title":"Cancer Res"},{"key":"10.1016\/j.drudis.2026.104820_b0315","unstructured":"Cherney E, et al. BMS-986482: An Immuno-oncology Optimized CELMoD Pan-Degrader of IKZF1\u20134 for the Treatment of Solid Tumors. ACS Spring First-Time Disclosures. 2026. Accessed September 9, 2026. https:\/\/acs.digitellinc.com\/p\/s\/bms-986482-an-immuno-oncology-optimized-celmods-pan-degrader-of-ikzf1-4-for-the-treatment-of-solid-tumors-651599 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0320","unstructured":"ClinicalTrials.gov. A Study of BMS-986449 With and Without Nivolumab in Participants With Advanced Solid Tumors. NCT05888831. https:\/\/clinicaltrials.gov\/study\/NCT05888831 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0325","unstructured":"ClinicalTrials.gov. A Study of BMS-986482 Alone or as Combination Therapy in Participants With Advanced Solid Tumors. NCT06697197. https:\/\/clinicaltrials.gov\/study\/NCT06697197 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0330","doi-asserted-by":"crossref","first-page":"20596","DOI":"10.1021\/acs.jmedchem.6c01271","article-title":"Discovery of BMS-986449: a potent, selective degrader of the transcription factors IKZF2 (Helios) and IKZF4 (Eos) to target regulatory T cells in solid tumors","volume":"69","author":"Cherney","year":"2026","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2026.104820_b0335","unstructured":"American Chemical Society. KFA115: A First-in-Class Selective IKZF2 (Helios) and IKZF4 (Eos) Molecular Glue Degrader for Immuno-Oncology. https:\/\/acs.digitellinc.com\/p\/s\/kfa115-a-first-in-class-selective-ikzf2-helios-and-ikzf4-eos-molecular-glue-degrader-for-immuno-oncology-666870 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0340","unstructured":"ClinicalTrials.gov. A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers. NCT05544929. 2026. https:\/\/clinicaltrials.gov\/study\/NCT05544929 [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0345","unstructured":"Chen Z, et al. IKZF2 degraders and uses thereof. International patent WO2023183540A1. https:\/\/patents.google.com\/patent\/WO2023183540A1\/en [Accessed September 26, 2026]."},{"key":"10.1016\/j.drudis.2026.104820_b0350","doi-asserted-by":"crossref","first-page":"9615","DOI":"10.1021\/acs.jmedchem.6c00500","article-title":"Discovery of highly potent and selective IKZF2 degraders for cancer immunotherapy","volume":"69","author":"Wang","year":"2026","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2026.104820_b0355","doi-asserted-by":"crossref","first-page":"16237","DOI":"10.1021\/acs.jmedchem.5c01086","article-title":"Discovery of novel potent triple IKZF1\/2\/3 degraders for the treatment of hematological cancers","volume":"68","author":"Wei","year":"2025","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2026.104820_b0360","doi-asserted-by":"crossref","DOI":"10.1002\/cbic.202400365","article-title":"IKZF2 Degradation: it's time to take into account it when designing Cereblon-based PROTACs","volume":"25","author":"Li","year":"2024","journal-title":"Chembiochem"},{"key":"10.1016\/j.drudis.2026.104820_b0365","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2418985122","article-title":"Anti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1","volume":"122","author":"Mok","year":"2025","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2026.104820_b0370","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1021\/acs.jmedchem.5c00076","article-title":"Leveraging structural and computational biology for molecular glue discovery","volume":"68","author":"Kang","year":"2025","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2026.104820_b0375","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1182\/blood.2020007081","article-title":"Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma","volume":"137","author":"Gooding","year":"2021","journal-title":"Blood"},{"key":"10.1016\/j.drudis.2026.104820_b0380","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1182\/blood-2018-05-852798","article-title":"Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice","volume":"132","author":"Fink","year":"2018","journal-title":"Blood"},{"key":"10.1016\/j.drudis.2026.104820_b0385","doi-asserted-by":"crossref","first-page":"11802","DOI":"10.1073\/pnas.1814446115","article-title":"Humanized cereblon mice revealed two distinct therapeutic pathways of immunomodulatory drugs","volume":"115","author":"Gemechu","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2026.104820_b0390","doi-asserted-by":"crossref","DOI":"10.1172\/JCI153514","article-title":"Degradation of GSPT1 causes TP53-independent cell death in leukemia while sparing normal hematopoietic stem cells","volume":"132","author":"Sellar","year":"2022","journal-title":"J Clin Invest"}],"container-title":["Drug Discovery Today"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644626002254?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644626002254?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:47:59Z","timestamp":1792856879000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1359644626002254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":78,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["S1359644626002254"],"URL":"https:\/\/doi.org\/10.1016\/j.drudis.2026.104820","relation":{},"ISSN":["1359-6446"],"issn-type":[{"value":"1359-6446","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting IKZF2 with molecular glue degraders for cancer immunotherapy","name":"articletitle","label":"Article Title"},{"value":"Drug Discovery Today","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.drudis.2026.104820","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"104820"}}