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Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Open accessAbstract
Drug With a (Re)Purpose: Thalidomide, once infamous for its deleterious effects on fetal development, has re-emerged as a drug of great interest because of its beneficial immunomodulatory effects. A derivative drug called lenalidomide significantly extends the survival of patients with multiple myeloma, but the molecular mechanisms underlying its efficacy remain unclear (see the Perspective by Stewart ). Building on a previous observation that thalidomide binds to cereblon, a ubiquitin ligase, Lu et al. (p. 305 , published online 28 November) and Krönke et al. (p. 301 , published online 28 November) show that in the presence of lenalidomide, cereblon selectively targets two B cell transcription factors (Ikaros family members, IKZF1 and IKZF3) for degradation. In myeloma cell lines and patient cells, down-regulation of IKZF1 and IKZF3 was necessary and sufficient for the drug's anticancer activity. Thus, lenalidomide may act, at least in part, by “grepurposing” a ubiquitin ligase.
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In the citing paper
“Thalidomide analogues recruit zinc-finger transcription factors and other targets to CRBN8–11, the substrate receptor of the cullin-RING E3 ubiquitin ligase CUL4A/B-RBX1-DDB1-CRBN (CRL4CRBN)12.”
From The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K (2020) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The small molecules thalidomide, lenalidomide, and pomalidomide induce the ubiquitination and proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by recruiting a Cys2-His2 (C2H2) zinc finger domain to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase.”
From Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN (2018) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thalidomide analogs bind Cereblon (CRBN), the substrate receptor of the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase and alter its substrate selectivity to recruit, ubiquitinate and degrade seemingly unrelated proteins including Ikaros (IKZF1), Aiolos (IKZF3), Casein kinase 1 alpha (CK1α) and GSPT1 (2–7).”
From Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN (2018) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“proteome-wide mass-spectrometry demonstrated selective degradation of endogenous IKZF1/3, and ZFP91 in multiple cell lines (3, 4, 16).”
From Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN (2018) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thalidomide, lenalidomide and pomalidomide mediate CRL4CRBN-dependent degradation of a larger number of proteins than previously appreciated through a C2H2 ZF degron (3, 4, 16).”
From Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN (2018) · cites this paper as [3]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“their recruitment to cRl4 cRBN , upon lenalidomide treatment, led to their selective ubiquitylation and proteasomal degradation, ablating their role at promoters of their target genes (Krönke et al. 2014;lu et al. 2014).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Krönke et al. 2014
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both thalidomide and lenalidomide lack specificity for iKZF2 (Krönke et al. 2014;lu et al. 2014), as it encodes a histidine in a critical thalidomidebinding position.”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Krönke et al. 2014
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mechanistic studies later confirmed that the efficacy of lenalidomide in 5q-MDS was actually due to the recruitment of an unexpected neo-substrate: the kinase cK1α (CSNK1A1) which resides within the long arm of chromosome 5 (5q32) (Krönke et al. 2014) (Figure 5B, i).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Krönke et al. 2014
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“IMiDs bind to cereblon and activate cereblon E3 ligase activity, resulting in the rapid ubiquitination and degradation of two specific B cell transcription factors, Ikaros family zinc finger proteins Ikaros (IKZF 1) and Aiolos (IKZF3).77–79”
From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [78]
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In the citing paper
“lenalidomide was shown to promote the interaction between cRBN and two members of the ikaros transcription factor family: iKZF1 and iKZF3 (gandhi et al. 2014;Krönke et al. 2014;lu et al. 2014).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Krönke et al. 2014
The cited source says what the claim attributes to it.
In the citing paper
“As such, lenalidomide can promote the interaction between cRl4 cRBN and both iKZF1 and iKZF3 resulting in their selective degradation which disrupts their role at gene promoters (Krönke et al. 2014;lu et al. 2014).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Krönke et al. 2014
In the citing paper
“These compounds, collectively known as immunomodulatory drugs (IMiDs), can promote the degradation of a host of cellular proteins by extending the subpar interfaces they form with CRBN, the substrate receptor of the CUL4-RBX1-DDB1 (CRL4) ubiquitin ligase complex9–20.”
From Defining molecular glues with a dual-nanobody cannabidiol sensor (2022) · cites this paper as [10]
In the citing paper
“As described before, in the presence of IMiDs, CRBN E3 ligase induces the proteasomal degradation of a set neo-substrates, such as IKZF1/3[13,39], CK1α[40] and GSPT1[15].”
From Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries (2021) · cites this paper as [13]
In the citing paper
“This is further supported by the observations that PZ could selectively induce Bcl-xl but not Bcl-2 poly-ubiquitination and had no significant effect on the expression of the CRBN native substrate, glutamine synthetase (GS)36, and its neosubstrates recruited by thalidomide and its analogues including CK1α37, IKZF1, and IKZF3 (ref. 38) (Supplementary Fig. 1 f, g).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [38]
In the citing paper
“In brief, IMiDs bind the E3 ligase cereblon (CRBN), thus complementing a surface patch that subsequently recruits a variety of C2H2 zinc finger transcription factors for ubiquitination and degradation.48−51”
From Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence (2023) · cites this paper as [50]
In the citing paper
“In brief, IMiDs were first shown to trigger CRBN-dependent proteasomal degradation of the C2H2-type zing-finger transcription factors Ikaros (IKZF1) and Aiolos (IKZF3).[46][47][48]”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [47]
In the citing paper
“The presence of a glutamine residue in their second zing-finger domain enables IMiD-induced degradation, 47 while the histidine residues in Helios (IKZF2) do not.”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [47]
In the citing paper
“thalidomide interacts with CRBN to form a novel surface, resulting in interactions with neosubstrates such as Ikaros (IKZF1) and Aiolos (IKZF3) and their ubiquitination and subsequent proteasomal degradation.20,21”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [20]
In the citing paper
“lenalidomide and pomalidomide induce CRBN-dependent ubiquitination and degradation of Ikaros and Aiolos, transcription factors required for the development of lymphoids and survival of multiple myeloma8–10.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [8]
In the citing paper
“Molecular glues, based on the serendipitous discovery that thalidomide and its analogues act as degrader molecules, constitute another important therapeutic class1–8.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [4]
In the citing paper
“These drugs co-opt CRBN to target IKAROS family zinc finger 1 (IKZF1) and IKZF3 for degradation3,4,24, and are now considered as pioneering examples of molecular glues.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [4]
In the citing paper
“CRBN appears to be emerging as a preferred E3 ligase for the first wave of TPD therapeutics in clinical trials.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [4]
In the citing paper
“Examples here include the approved IMiD class, which relies on CRBN to degrade IKZF1/IKZF3 (refs4,5) via a molecular glue mechanism”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [4]
In the citing paper
“thalidomide and its analogues do not inhibit the enzymatic activity of CRL4CRBN, but instead confer neomorphic activity on CRBN to mediate the selective ubiquitination and resultant proteasomal degradation of the transcription factors Ikaros family zinc finger protein 1 (IKZF1) and IKZF3 (Aiolos) in MM cells and T cells11–13.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [11]
In the citing paper
“In 2013, thalidomide analogues were discovered to exert their therapeutic effects by acting as a molecular glue to recruit disease-relevant neosubstrate proteins to an E3 ubiquitin ligase, resulting in neosubstrate ubiquitination and, ultimately, proteasomal degradation11–13.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [11]
In the citing paper
“given that proteasome inhibitors antagonize lenalidomide-induced protein degradation11,12,55.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [11]
In the citing paper
“Most known neosubstrate proteins have been identified through proteomic analyses of different cell lineages11,15,165,166.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [11]
In the citing paper
“Ebert's gourp and Kaelin Jr's group independently demonstrated that when lenalidomide binds to CRBN, a new function of CRBN is induced, namely, to ubiquitinate and degrade Ikaros (IKZF1) and Aiolos (IKZF3), which are transcription factors that are known to be responsible for the maturation of B cells [25,26].”
From Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs (2016) · cites this paper as [25]
In the citing paper
“CRBN was shown to bind the drug thalidomide in its substrate binding pocket, thereby creating a new surface to recruit other proteins for ubiquitination and degradation, such as the transcription factors Ikaros and Aiolos (IKZF1 and 3, respectively) or the kinase CK1α [70–72].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [72]
In the citing paper
“The clinical efficacy of IMiDs is driven at least in part by their capacity to induce CRBN-mediated degradation of neo-substrates: cancer cells become resistant to the multiple myeloma IMiD drug lenalidomide upon mutation of a single amino acid in IKFZ3 that rescues this transcription factor from proteolytic degradation 7 ;”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [7]
In the citing paper
“cancer cells become resistant to the multiple myeloma IMiD drug lenalidomide upon mutation of a single amino acid in IKFZ3 that rescues this transcription factor from proteolytic degradation 7 ;”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [7]
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Cites
Rappsilber, J., Mann, M., & Ishihama, Y. (2007) · Nature Protocols · doi:10.1038/nprot.2007.261 · Cited by 4,641
RING Domain E3 Ubiquitin Ligases
Deshaies, R. J., & Joazeiro, C. A. P. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.101807.093809 · Cited by 2,679
Identification of a Primary Target of Thalidomide Teratogenicity
Ito, T., Ando, H., Suzuki, T., Ogura, T., Hotta, K., Imamura, Y., Yamaguchi, Y., & Handa, H. (2010) · Science · doi:10.1126/science.1177319 · Cited by 2,136
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., Brownell, J. E., Burke, K. E., Cardin, D. P., Critchley, S., et al. (2009) · Nature · doi:10.1038/nature07884 · Cited by 1,990
Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia
Mullighan, C. G., Goorha, S., Radtke, I., Miller, C. B., Coustan‐Smith, E., Dalton, J., Girtman, K., Mathew, S., Ma, J., Pounds, S. B., et al. (2007) · Nature · doi:10.1038/nature05690 · Cited by 1,777
Mechanism of auxin perception by the TIR1 ubiquitin ligase
Tan, X., Calderon-Villalobos, L. I. A., Sharon, M., Zheng, C., Robinson, C. V., Estelle, M., & Zheng, N. (2007) · Nature · doi:10.1038/nature05731 · Cited by 1,688
Sampaio, E. P., Sarno, E. N., Gallily, R., Cohn, Z. A., & Kaplan, G. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.3.699 · Cited by 1,191
The ikaros gene is required for the development of all lymphoid lineages
Georgopoulos, K., Bigby, M., Wang, J.-H., Molnar, A., Wu, P., Winandy, S., & Sharpe, A. (1994) · Cell · doi:10.1016/0092-8674(94)90407-3 · Cited by 985
A practical recipe for stable isotope labeling by amino acids in cell culture (SILAC)
Ong, S., & Mann, M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.427 · Cited by 917
Lopez-Girona, A., Mendy, D., Ito, T., Miller, K., Gandhi, A. K., Kang, J., Karasawa, S., Carmel, G., Jackson, P., Abbasian, M., et al. (2012) · Leukemia · doi:10.1038/leu.2012.119 · Cited by 814
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Targeting the Ubiquitin System in Glioblastoma
Scholz, N., Kurian, K. M., Siebzehnrübl, F. A., & Licchesi, J. D. F. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.574011 · Cited by 37
A novel Cereblon E3 ligase modulator with antitumor activity in gastrointestinal cancer
Lier, S., Sellmer, A., Orben, F., Heinzlmeir, S., Krauß, L., Schneeweis, C., Hassan, Z., Schneider, C., Patricia Gloria Schäfer, A., Pongratz, H., et al. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105505 · Cited by 37
A small-molecule VHL molecular glue degrader for cysteine dioxygenase 1
Tutter, A., Buckley, D., Golosov, A. A., Ma, X., Shu, W., McKay, D. J. J., Darsigny, V., Dovala, D., Beckwith, R., Solomon, J., et al. (2025) · Nature Chemical Biology · doi:10.1038/s41589-025-01936-x · Cited by 36
Tateno, S., Iida, M., Fujii, S., Suwa, T., Katayama, M., Tokuyama, H., Yamamoto, J., Ito, T., Sakamoto, S., Handa, H., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61027-w · Cited by 36
Molecular glue degraders: exciting opportunities for novel drug discovery
Lemaitre, T., Cornu, M., Schwalen, F., Since, M., Kieffer, C., & Voisin-Chiret, A. S. (2024) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2024.2306845 · Cited by 36
Drug Discovery Approaches to Target E3 Ligases
Rodríguez-Gimeno, A., & Galdeano, C. (2024) · ChemBioChem · doi:10.1002/cbic.202400656 · Cited by 39
Targeted degradation of extracellular proteins: state of the art and diversity of degrader designs
Mamun, M. A. A., Bakunts, A. G., & Chernorudskiy, A. L. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01703-4 · Cited by 41
Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera
Kim, K., Lee, D.-H., Park, S., Jo, S.-H., Ku, B., Park, S. G., Park, B. C., Jeon, Y. U., Ahn, S., Kang, C. H., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-56177-5 · Cited by 37
Role of the Bone Marrow Milieu in Multiple Myeloma Progression and Therapeutic Resistance
Ho, M., Goh, C. Y., Patel, A. S., Staunton, S., O’Connor, R., Godeau, M., & Bianchi, G. (2020) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2020.05.026 · Cited by 40
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Gama-Brambila, R. A., Chen, J., Zhou, J., Tascher, G., Münch, C., & Cheng, X. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.04.018 · Cited by 37
Zhou, B., Zhou, H., Xu, L., Cai, R., Chen, C., Chi, B., & Tuo, X. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106017 · Cited by 36
IRF4 as an Oncogenic Master Transcription Factor
Wong, R. W. J., Ong, J. Z. L., Theardy, M. S., & Sanda, T. (2022) · Cancers · doi:10.3390/cancers14174314 · Cited by 39
Krasavin, M., Adamchik, M., Bubyrev, A. I., Heim, C., Maiwald, S. A., Zhukovsky, D., Zhmurov, P. A., Bunev, A. S., & Hartmann, M. D. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114990 · Cited by 36
Transcriptional control of ILC identity
Korchagina, A. A., Shein, S. A., Koroleva, E. P., & Tumanov, A. V. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1146077 · Cited by 36
Roy, A. L., Prébet, T., Castellano, R., Goubard, A., Riccardi, F., Fauriat, C., Granjeaud, S., Benyamine, A., Castanier, C., Orlanducci, F., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00977 · Cited by 35
Neri, P. E., Barwick, B. G., Jung, D., Patton, J. C., Maity, R., Tagoug, I., Stein, C. K., Tilmont, R., Leblay, N., Ahn, S., et al. (2023) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-23-0061 · Cited by 35
Goh, W., Sudholz, H., Foroutan, M., Scheer, S., Pfefferle, A., Delconte, R. B., Meng, X., Shen, Z., Hennessey, R., Kong, I. Y., et al. (2024) · Nature Immunology · doi:10.1038/s41590-023-01718-4 · Cited by 39
CAR-T therapy and targeted treatments: Emerging combination strategies in solid tumors
Liu, J., Jiao, X., Ma, D., Fang, Y., & Gao, Q. (2024) · Med · doi:10.1016/j.medj.2024.03.001 · Cited by 35
Ramberger, E., Sapozhnikova, V., Ng, Y. L. D., Dolnik, A., Ziehm, M., Popp, O., Sträng, E., Kull, M., Grünschläger, F., Krüger, J., et al. (2024) · Nature Cancer · doi:10.1038/s43018-024-00784-3 · Cited by 47
Self-citationZhang, H., Luo, X.-J., Yang, W., Wu, Z., Zhao, Z., Pei, X., Zhang, X., Chen, C., Lei, J. H., Shi, Q., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53997-6 · Cited by 37
SE(3)-equivariant ternary complex prediction towards target protein degradation
Xue, F., Zhang, M. L., Li, S., Gao, X., Wohlschlegel, J. A., Huang, W., Yang, Y., & Deng, W. (2025) · Nature Communications · doi:10.1038/s41467-025-61272-5 · Cited by 44
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Ma, Z., Zhou, M., Chen, H., Shen, Q., & Zhou, J. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02975 · Cited by 43
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Butterfield, G. L., Reisman, S. J., Iglesias, N., & Gersbach, C. A. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.04.004 · Cited by 43
IRF4 Mediates the Oncogenic Effects of STAT3 in Anaplastic Large Cell Lymphomas
Bandini, C., Pupuleku, A., Spaccarotella, E., Pellegrino, E., Wang, R., Vitale, N., Duval, C., Cantarella, D., Rinaldi, A., Provero, P., et al. (2018) · Cancers · doi:10.3390/cancers10010021 · Cited by 36
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Derenzini, E., Mondello, P., Erazo, T., Portelinha, A., Liu, Y., Scallion, M. I., Asgari, Z., Philip, J., Hilden, P. D., Valli, D., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.055 · Cited by 35
Ligand-induced genetic degradation as a tool for target validation
Yesbolatova, A., Tominari, Y., & Kanemaki, M. T. (2018) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2018.11.001 · Cited by 35
Jackson, G. H., Davies, F. E., Pawlyn, C., Cairns, D. A., Striha, A., Collett, C., Waterhouse, A., Jones, J. R., Kishore, B., Garg, M. K., et al. (2020) · Haematologica · doi:10.3324/haematol.2020.247130 · Cited by 36
Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler
Liwocha, J., Krist, D. T., van Noort, G. J. V. D. H., Hansen, F. M., Truong, V. H., Karayel, Ö., Purser, N., Houston, D., Burton, N., Bostock, M. J., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-00696-0 · Cited by 37
Ward, J. P., Berrien-Elliott, M. M., Gomez, F., Luo, J. R., Becker‐Hapak, M., Cashen, A. F., Wagner‐Johnston, N. D., Maddocks, K. J., Mosior, M., Foster, M., et al. (2021) · Blood · doi:10.1182/blood.2021011894 · Cited by 35
Zheng, L., Feng, Z., Tao, S., Gao, J., Lin, Y., Wei, X., Zheng, B., Huang, B. H., Zheng, Z., Zhang, X., et al. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.652 · Cited by 34
SJPYT-195: A Designed Nuclear Receptor Degrader That Functions as a Molecular Glue Degrader of GSPT1
Huber, A. D., Li, Y., Lin, W., Galbraith, A. N., Mishra, A., Porter, S. N., Wu, J., Gee, R. R. F., Zhuang, W., Pruett‐Miller, S. M., et al. (2022) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.2c00223 · Cited by 34
CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma
Barankiewicz, J., Salomon‐Perzyński, A., Misiewicz-Krzemińska, I., & Lech‐Marańda, E. (2022) · Cancers · doi:10.3390/cancers14184492 · Cited by 38
Mark, K. G., Loveless, T. B., & Toczyski, D. P. (2016) · Nature Protocols · doi:10.1038/nprot.2016.008 · Cited by 34
Key Considerations in Targeted Protein Degradation Drug Discovery and Development
Qin, L., Dai, H., & Wang, J. (2022) · Frontiers in Chemistry · doi:10.3389/fchem.2022.934337 · Cited by 35
What influences the activity of Degrader−Antibody conjugates (DACs)
Guo, Y., Li, X., Xie, Y., & Wang, D. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116216 · Cited by 38
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Neigenfind, P., Massaro, L., Péter, Á., Degnan, A. P., Emmanuel, M. A., Oderinde, M. S., He, C., Peters, D., Ewing, T. E., Kawamata, Y., et al. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202319856 · Cited by 34
Targeting and tracking mRNA lipid nanoparticles at the particle, transcript and protein level
Kang, D. D., Marks, A. R., Morlà‐Folch, J., Dong, Y., Brown, B. D., & Teunissen, A. J. P. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01511-8 · Cited by 40
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Shi, C.-X., Kortüm, K. M., Zhu, Y. X., Jedlowski, P. M., Bruins, L. A., Braggio, E., & Stewart, A. K. (2015) · Haematologica · doi:10.3324/haematol.2015.124297 · Cited by 34
Translating the anti-myeloma activity of Natural Killer cells into clinical application
Fionda, C., Stabile, H., Molfetta, R., Soriani, A., Bernardini, G., Zingoni, A., Gismondi, A., Paolini, R., Cippitelli, M., & Santoni, A. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.10.005 · Cited by 34
Unraveling the mysteries of plasma cells
Schuh, W., Mielenz, D., & Jäck, H. (2020) · Advances in immunology · doi:10.1016/bs.ai.2020.01.002 · Cited by 38
Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy
Wirth, M., Schick, M., Keller, U. B., & Krönke, J. (2020) · Cancers · doi:10.3390/cancers12123764 · Cited by 35
Self-citationVascular Impact of Cancer Therapies: The Case of BTK (Bruton Tyrosine Kinase) Inhibitors
Fleming, M. R., Xiao, L., Jackson, K. D., Beckman, J. A., Barac, A., & Moslehi, J. J. (2021) · Circulation Research · doi:10.1161/circresaha.121.318259 · Cited by 36
Ligand-induced degrons for studying nuclear functions
Kanemaki, M. T. (2022) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2021.12.006 · Cited by 35
PU.1 acts as tumor suppressor for myeloma cells through direct transcriptional repression of IRF4
Ueno, N., Nishimura, N., Ueno, S., Endo, S., Tatetsu, H., Hirata, S., Hata, H., Matsuoka, M., Mitsuya, H., & Okuno, Y. (2017) · Oncogene · doi:10.1038/onc.2017.79 · Cited by 34
Identification and characterization of cancer vulnerabilities via targeted protein degradation
Mayor-Ruiz, C., & Winter, G. E. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2018.12.003 · Cited by 33
Implications of frequent hitter E3 ligases in targeted protein degradation screens
Zhang, X., Simon, G. M., & Cravatt, B. F. (2025) · Nature Chemical Biology · doi:10.1038/s41589-024-01821-z · Cited by 36
Tuning the proteasome to brighten the end of the journey
Mayor, T., Sharon, M., & Glickman, M. H. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00198.2016 · Cited by 32
The ubiquitin ligase STUB1 regulates stability and activity of RUNX1 and RUNX1–RUNX1T1
Yonezawa, T., Takahashi, H., Shikata, S., Liu, X., Tamura, M., Asada, S., Fukushima, T., Fukuyama, T., Tanaka, Y., Sawasaki, T., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.785675 · Cited by 33
Tan, L., & Gray, N. S. (2018) · Chinese Journal of Chemistry · doi:10.1002/cjoc.201800293 · Cited by 34
Xiao, D., Wang, Y.-J., Hu, X., Kan, W., Zhang, Q., Jiang, X., Zhou, Y., Li, J. X., & Lu, W. P. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.035 · Cited by 32
Yokoo, H., Shibata, N., Endo, A., Ito, T., Yanase, Y., Murakami, Y., Fujii, K., Hamamura, K., Saeki, Y., Naito, M., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01206 · Cited by 33
Natural Killer Cells in the Malignant Niche of Multiple Myeloma
Venglár, O., Bago, J., Motais, B., Hájek, R., & Jelı́nek, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.816499 · Cited by 34
Miñarro-Lleonar, M., Bertran‐Mostazo, A., Duro, J., Barril, X., & Juárez‐Jiménez, J. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01692 · Cited by 31
Bourgeois, W., Cutler, J. A., Aubrey, B. J., Wenge, D. V., Perner, F., Martucci, C., Henrich, J. A., Klega, K. S., Nowak, R. P., Donovan, K. A., et al. (2023) · Blood · doi:10.1182/blood.2023021105 · Cited by 32
Self-citationCryo-electron microscopy-based drug design
Cebi, E., Lee, J., Subramani, V. K., Bak, N., Oh, C., & Kim, K. K. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2024.1342179 · Cited by 34
Unbiased mapping of cereblon neosubstrate landscape by high-throughput proteomics
Steger, M., Nishiguchi, G., Wu, Q., Schwalb, B., Shashikadze, B., McGowan, K., Actis, M., Aggarwal, A., Shi, Z., Price, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62829-0 · Cited by 32
Costa, L. J., Fanning, S. R., Stephenson, J., Afrin, L. B., Kistner‐Griffin, E., Bentz, T. A., & Stuart, R. K. (2014) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2014.935369 · Cited by 32
Small molecule-mediated protein knockdown as a new approach to drug discovery
Tinworth, C. P., Lithgow, H., & Churcher, I. (2016) · MedChemComm · doi:10.1039/c6md00347h · Cited by 32
Costa, F., Vescovini, R., Bolzoni, M., Marchica, V., Storti, P., Toscani, D., Accardi, F., Notarfranchi, L., Palma, B. D., Manferdini, C., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18085 · Cited by 32
Bastea, L. I., Liou, G., Pandey, V., Martinez, A. K. F., Roemeling, C. A. V., Döppler, H. R., Li, Z., Qiu, Y., Edenfield, B. H., Copland, J. A., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-1153 · Cited by 32
Targeted Protein Degradation: Clinical Advances in the Field of Oncology
Salama, A. K. A. A., Trkulja, M. V., Casanova, E., & Uras, I. Z. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315440 · Cited by 36
Affinity purification in target identification: the specificity challenge
Zheng, W., Li, G., & Li, X. (2015) · Archives of Pharmacal Research · doi:10.1007/s12272-015-0635-2 · Cited by 33
Self-citationJonasova, A., Bokorova, R., Polak, J., Vostry, M., Kostecka, A., Hajkova, H., Neuwirtova, R., Siskova, M., Sponerova, D., Cermak, J., et al. (2015) · European Journal of Haematology · doi:10.1111/ejh.12457 · Cited by 31
Design and Development of IKZF2 and CK1α Dual Degraders
Miyamoto, D. K., Curnutt, N. M., Park, S., Stavropoulos, A., Kharas, M. G., & Woo, C. M. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01736 · Cited by 31
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Shabek, N., Ruble, J., Waston, C. J., Garbutt, K. C., Hinds, T. R., Li, T., & Zheng, N. (2018) · Cell Discovery · doi:10.1038/s41421-018-0064-8 · Cited by 29
Small-molecule PROTACs: Novel Agents for Cancer Therapy
Wan, Y., Yan, C., Gao, H. J., & Liu, T. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0340 · Cited by 32
Zhao, M., Hu, M., Chen, Y., Liu, H., Chen, Y., Liu, B., & Fang, B. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.02.110 · Cited by 29
Novel Experimental Drugs for Treatment of Multiple Myeloma
Offidani, M., Corvatta, L., Morè, S., & Olivieri, A. (2021) · Journal of Experimental Pharmacology · doi:10.2147/jep.s265288 · Cited by 32
Discovery of Molecular Glue Degraders via Isogenic Morphological Profiling
Ng, A., Offensperger, F., Cisneros, J. A., Scholes, N. S., Malik, M., Villanti, L., Rukavina, A., Ferrada, E., Hannich, J. T., Koren, A., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.3c00598 · Cited by 31
A biotin targeting chimera (BioTAC) system to map small molecule interactomes in situ
Tao, A. J., Jiang, J., Gadbois, G. E., Goyal, P., Boyle, B. T., Mumby, E. J., Myers, S. A., English, J. G., & Ferguson, F. M. (2023) · Nature Communications · doi:10.1038/s41467-023-43507-5 · Cited by 35
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Dhodapkar, M. V., & Dhodapkar, K. M. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.05.009 · Cited by 32
McGraw, K. L., Basiorka, A. A., Johnson, J., Clark, J., Cáceres, G., Padron, E., Heaton, R., Ozawa, Y., Wei, S., Sokol, L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114249 · Cited by 31
Structural Dynamics of the Cereblon Ligand Binding Domain
Hartmann, M. D., Boichenko, I., Coles, M., Lupas, A. N., & Hernandez Alvarez, B. (2015) · PLOS ONE · doi:10.1371/journal.pone.0128342 · Cited by 31
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Rodriguez-Rivera, F. P., & Levi, S. M. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00389 · Cited by 30
SuFEx-based chemical diversification for the systematic discovery of CRBN molecular glues
Carter, T. R., Milosevich, N., Dada, L., Shaum, J. B., Sharpless, K. B., Kitamura, S., & Erb, M. A. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117699 · Cited by 31
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Shaum, J. B., Ordoño, M. M. I., Steen, E. A., Wenge, D. V., Cheong, H., Janowski, J., Hunkeler, M., Bilotta, E. M., Rutter, Z. J., Barta, P. A., et al. (2026) · Nature Chemical Biology · doi:10.1038/s41589-025-02137-2 · Cited by 41
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Guirguis, A. A., & Ebert, B. L. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.10.004 · Cited by 30
Self-citationDimopoulos, K., Munch‐Petersen, H. F., Eskelund, C. W., Sjø, L. D., Ralfkiaer, E. M., Gimsing, P., & Grønbæk, K. (2018) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2018.1466290 · Cited by 29
AMPK is down‐regulated by the CRL4A‐CRBN axis through the polyubiquitination of AMPKα isoforms
Kwon, E., Li, X., Deng, Y., Chang, H. W., & Kim, D. Y. (2019) · The FASEB Journal · doi:10.1096/fj.201801766rrr · Cited by 30
Self-citationImmunomodulatory drugs in the treatment of multiple myeloma
Abe, Y., & Ishida, T. (2019) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyz083 · Cited by 30
Kim, M., Min, Y., Shim, J., Chun, E., & Lee, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02203 · Cited by 30
Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4
Ochiai, K., Yamaoka, M., Swaminathan, A., Shima, H., Hiura, H., Matsumoto, M., Kurotaki, D., Nakabayashi, J., Funayama, R., Nakayama, K., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108517 · Cited by 29
Yao, H. W., Xie, W., Dai, Y., Liu, Y., Gu, W., Li, J., Wu, L., Xie, J., Rui, W., Ren, B., et al. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac053 · Cited by 30
Self-citationUbiquitinomics: History, methods, and applications in basic research and drug discovery
Steger, M., Karayel, Ö., & Demichev, V. (2022) · PROTEOMICS · doi:10.1002/pmic.202200074 · Cited by 30
Millrine, D., Miyata, H., Tei, M., Dubey, P. K., Nyati, K. K., Nakahama, T., Gemechu, Y., Ripley, B., & Kishimoto, T. (2016) · International Immunology · doi:10.1093/intimm/dxw005 · Cited by 30
An IMiD-induced SALL4 degron system for selective degradation of target proteins
Yamanaka, S., Shoya, Y., Matsuoka, S., Nishida-Fukuda, H., Shibata, N., & Sawasaki, T. (2020) · Communications Biology · doi:10.1038/s42003-020-01240-5 · Cited by 29
Patil, A., Manzano, M., & Gottwein, E. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019031732 · Cited by 29
Discovery of AK-1690: A Potent and Highly Selective STAT6 PROTAC Degrader
Kaneshige, A., Yang, Y., Bai, L., Wang, M., Xu, R., Mallik, L., Chinnaswamy, K., Metwally, H., Wang, Y., McEachern, D., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01009 · Cited by 31
Unleashing the Power of Covalent Drugs for Protein Degradation
Fu, M., Jin, H., Wang, S., Shen, L., Liu, H., Liu, Y., Zheng, Y., & Dai, X. (2025) · Medicinal Research Reviews · doi:10.1002/med.22101 · Cited by 31
Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41
Basiorka, A. A., McGraw, K. L., Ceuninck, L. D., Griner, L. N., Zhang, L., Clark, J., Cáceres, G., Sokol, L., Komrokji, R. S., Reuther, G. W., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1756 · Cited by 30
Bhutani, M., Zhang, Q., Friend, R. N., Voorhees, P. M., Druhan, L. J., Barlogie, B., Sonneveld, P., Morgan, G. J., Symanowski, J. T., Avalos, B. R., et al. (2017) · The Lancet Haematology · doi:10.1016/s2352-3026(17)30143-6 · Cited by 29
IMiD compounds affect CD34+ cell fate and maturation via CRBN-induced IKZF1 degradation
Li, S., Fu, J., Wang, H., Ma, H., Xu, X., Yang, Y., Deng, S., Mapara, M. Y., & Lentzsch, S. (2018) · Blood Advances · doi:10.1182/bloodadvances.2017010348 · Cited by 30
PD-L1 upregulation in myeloma cells by panobinostat in combination with interferon-γ
Iwasa, M., Harada, T., Oda, A., Bat‐Erdene, A., Teramachi, J., Tenshin, H., Ashtar, M., Oura, M., Sogabe, K., Udaka, K., et al. (2019) · Oncotarget · doi:10.18632/oncotarget.26726 · Cited by 30
Biological Background of Resistance to Current Standards of Care in Multiple Myeloma
Mogollón, P., Díaz-Tejedor, A., Algarín, E. M., Paíno, T., Garayoa, M., & Ocio, E. M. (2019) · Cells · doi:10.3390/cells8111432 · Cited by 30
Chernobrovkin, A. L., Cázares-Körner, C., Friman, T., Caballero, I. M., Amadio, D., & Molina, D. M. (2021) · SLAS DISCOVERY · doi:10.1177/2472555220984372 · Cited by 28
Ege, N., Bouguenina, H., Tatari, M. N., & Chopra, R. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.02.011 · Cited by 31
Yang, Z., Wu, X., Wei, Y., Polyanskaya, S. A., Iyer, S. V., Jung, M., Lach, F. P., Adelman, E. R., Klingbeil, O., Milazzo, J. P., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1542 · Cited by 31
Kikuchi, J., Kuroda, Y., Koyama, D., Osada, N., Izumi, T., Yasui, H., Kawase, T., Ichinohe, T., & Furukawa, Y. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2446 · Cited by 29
Kaushik, A., Parashar, S., Ambasta, R. K., & Kumar, P. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102279 · Cited by 30
Metadata
- Authors
- Krönke, J., Udeshi, N. D., Narla, A., Grauman, P., Hurst, S. N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., Ciarlo, C., Hartman, E., Munshi, N., Schenone, M., Schreiber, S. L., Carr, S. A., & Ebert, B. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Ebert, Benjamin L.
- ORCID
- Venue
- Science
- Published
- 2014-01-17
- Volume
- 343
- Issue
- 6168
- Pages
- 301-305
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4077049
- OpenAlex
- W2015345028
- Semantic Scholar
- bf4fc60d821257f664ef758f219b75586ad0adaa
- Cited by
- 1,879
- References
- 31
- Citations by year
- 2026: 159 · 2025: 188 · 2024: 185 · 2023: 169 · 2022: 176 · 2021: 196 · 2020: 186 · 2019: 138 · 2018: 125 · 2017: 100 · 2016: 102 · 2015: 88 · 2014: 59
- FWCI
- 37.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (5p01ca078378-15)
- National Heart, Lung, and Blood Institute (R01HL082945)
- National Human Genome Research Institute (RL1HG004671)
- National Cancer Institute (P01-CA078378, P50CA100707, P01CA108631, P01CA155258)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- lenalidomide, multiple myeloma, IKZF1, IKZF3, selective protein degradation, E3 ubiquitin ligase, ubiquitination, mechanism of action, IL-2 production, T cells, transcription factors
- MeSH terms
- Lenalidomide, Antineoplastic Agents, Humans, Interleukin-2, Multiple Myeloma, T-Lymphocytes, Thalidomide, Cell Line, Tumor, Ikaros Transcription Factor, Ubiquitination, HEK293 Cells, Proteolysis
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