Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS
Open accessAbstract
Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that lenalidomide induces the ubiquitination of casein kinase 1A1 (CK1α) by the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)), resulting in CK1α degradation. CK1α is encoded by a gene within the common deleted region for del(5q) MDS and haploinsufficient expression sensitizes cells to lenalidomide therapy, providing a mechanistic basis for the therapeutic window of lenalidomide in del(5q) MDS. We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding human residue enables lenalidomide-dependent degradation of CK1α. We further demonstrate that minor side chain modifications in thalidomide and a novel analogue, CC-122, can modulate the spectrum of substrates targeted by CRL4(CRBN). These findings have implications for the clinical activity of lenalidomide and related compounds, and demonstrate the therapeutic potential of novel modulators of E3 ubiquitin ligases.
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Proteome-wide mass spectrometry showed selective degradation of endogenous IKZF1/3 and ZFP91 in multiple cell lines.
“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 [4]
The Results section reports global mass-spectrometry profiling in KG-1 cells, and Extended Data Table 1 shows reduced IKZF1 and ZFP91 protein abundance after lenalidomide treatment. Extended Data Figure 8 also describes proteomic measurement of IKZF1 in MDS-L cells. The copy does not show mass-spectrometric degradation of endogenous IKZF3 or establish degradation of all three proteins across multiple cell lines; its IKZF3 assay used a luciferase reporter. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThalidomide, lenalidomide, and pomalidomide cause ubiquitination and proteasomal degradation of IKZF1 and IKZF3 by bringing a C2H2 zinc finger domain to CRBN, the substrate receptor of CRL4CRBN.
“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 [4]
The Discussion and Differential substrate specificity sections (pages not provided) state that all three drugs induce CRL4CRBN-mediated ubiquitination and degradation of IKZF1 and IKZF3. The copy mentions an IKZF1/3 degron but does not identify it as a C2H2 zinc finger domain or explicitly describe the degradation of these proteins as proteasomal. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThalidomide analogs bind CRBN and change its substrate selectivity so that it recruits, ubiquitinates, and degrades proteins including IKZF1, IKZF3, CK1α, and GSPT1.
“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 [4]
The CK1α-substrate and Differential substrate specificity sections (page unavailable) show that CRBN-binding thalidomide analogs can alter substrate selection: the paper reports degradation of IKZF1 and IKZF3 and demonstrates lenalidomide-dependent recruitment, ubiquitination, and degradation of CK1α. It also shows that the analogs differ in which substrates they affect. Our copy does not identify GSPT1 as a substrate (searched: GSPT1 and translation termination factor), so it does not support the full list. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThalidomide, lenalidomide, and pomalidomide mediate CRL4CRBN-dependent degradation of more proteins than previously appreciated through a C2H2 ZF degron.
“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 [4]
The Discussion and Differential substrate specificity sections report CRL4CRBN-mediated degradation of IKZF1 and IKZF3 by all three drugs and identify CK1α as an additional substrate strongly affected by lenalidomide, but not thalidomide. The CK1α is a substrate of CRL4CRBN section says its responsive region has no evident homology to the previously identified IKZF1/3 degron. The paper therefore does not support the claim that the expanded set of proteins is degraded through a C2H2 zinc-finger degron. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIMiDs can promote degradation of targets lacking a zinc finger domain, including CSNK1A1 and GSPT1.
“IMiDs can also promote degradation of targets that lack a zinc finger domain, including Casein Kinase 1 alpha (CSNK1A1) (Krönke et al., 2015; Petzold et al., 2016) and GSPT1 (Matyskiela et al., 2016).”
From Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome (2018) · cites this paper as Krönke et al., 2015
The “Lenalidomide induces degradation of CK1α” section reports that lenalidomide increases ubiquitination and decreases the abundance of CK1α, which is encoded by CSNK1A1. This supports the part of the sentence attributed to Krönke et al.; however, our copy does not explicitly state that CK1α lacks a zinc finger domain. The separate GSPT1 claim is attributed to another citation. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Expression of hsCRBN in mouse cells sensitizes cells to degradation of mmIKZF1/3, mmCSNK1A1, mmZFP91, or mmGZF1, but does not result in degradation of mmSALL4.
“Expression of hsCRBN in mouse cells, while sensitizing cells to degradation of IMiD targets such as mmIKZF1/3, mmCSNK1A1 (Krönke et al., 2015), mmZFP91, or mmGZF1 (Figure 4D,E), does not result in degradation of mmSALL4 (Figure 4F).”
From Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome (2018) · cites this paper as Krönke et al., 2015
The Species-specific effects of lenalidomide section reports that human CRBN expression enabled lenalidomide-dependent CK1α reduction in mouse Ba/F3 cells, supporting the mmCSNK1A1 part. Its IKZF1/3 results were obtained in human 293T cells, not mouse cells, so they do not establish degradation of mmIKZF1/3 under the claimed conditions. The ZFP91, GZF1, and SALL4 findings are attributed to the citing paper’s own figures, not to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredLenalidomide-induced degradation of the remaining CK1α mimics biallelic loss of CSNK1A1, which triggers p53 activation, enhances apoptosis and leads to clonal arrest of the 5q-deleted population, ultimately driving disease regression.
“However, lenalidomide-induced degradation of the remaining cK1α mimics biallelic loss of CSNK1A1 which triggers p53 activation, enhances apoptosis and leads to clonal arrest of the 5q-deleted population which ultimately drives disease regression (wei et al. 2009;Schneider et al. 2014;Krönke et al. 2015).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Krönke et al. 2015
The Discussion (page not available) says lenalidomide degrades CK1α below haploinsufficient levels in del(5q) MDS cells, inducing p53 activity and growth inhibition. The Species-specific effects section reports increased apoptosis and depletion of sensitized cells. These findings support the proposed mechanism, but the paper does not establish that it produces biallelic CSNK1A1 loss or directly demonstrate clonal arrest and disease regression in patients. (LLM, conf=0.84)
Experimental — accuracy not yet measuredLenalidomide treatment led to degradation of CSNK1A1.
“In accordance with previous findings, we also observed that treatment with lenalidomide led to degradation of CSNK1A1 (Krönke et al., 2015; Petzold et al., 2016).”
From Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome (2018) · cites this paper as Krönke et al., 2015
Mouse Crbn harbors a critical polymorphism that prevents IMiD-dependent degradation of ZnF substrates and CSNK1A1.
“Mouse Crbn harbors a critical polymorphism (Figure 4A,B and Figure 5) that prevents IMiD-dependent degradation of ZnF substrates and CSNK1A1 (Krönke et al., 2015), which could explain the absence of a SALL4-dependent phenotype in mice.”
From Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome (2018) · cites this paper as Krönke et al., 2015
Lenalidomide induces degradation of the kinase CK1a, whereas structurally similar thalidomide and pomalidomide do not.
“Shortly after, lenalidomide (Fig. 3D) was shown to also induce the degradation of the kinase CK1a, while the structurally similar thalidomide and pomalidomide do not.50”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [50]
Lenalidomide induces degradation of CK1α, a clinical target of 5q- syndrome.
“Lenalidomide also induces degradation of CK1α, a clinical target of 5q– syndrome11,12.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [11]
GSPT1, CK1α, and glutamine synthetase reside in the cytoplasm.
“The subcellular localizations of these factors differ: the transcription factors Ikaros, Aiolos, and MEIS2 are localized to the nucleus, whereas GSPT1, CK1α, and glutamine synthetase reside in the cytoplasm.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [11]
The transcription factors Ikaros, Aiolos, and MEIS2 are localized to the nucleus.
“The subcellular localizations of these factors differ: the transcription factors Ikaros, Aiolos, and MEIS2 are localized to the nucleus, whereas GSPT1, CK1α, and glutamine synthetase reside in the cytoplasm.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [11]
Over a dozen proteins, including Ikaros, Aiolos, GSPT1, CK1α, glutamine synthetase, MEIS2, KCNMA1/SLO1, CLC1, and AMPKα, have been identified as substrates for CRBN.
“To date, over a dozen proteins including Ikaros, Aiolos, GSPT1, CK1α, glutamine synthetase, MEIS2, KCNMA1/SLO1, CLC1, and AMPKα have been identified as substrates for CRBN3,11–16,24–28.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [11]
Molecular glues constitute another important therapeutic class of targeted protein degraders.
“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 [5]
The approved IMiD class relies on CRBN to degrade IKZF1/IKZF3 via a molecular glue mechanism.
“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 [5]
In del(5q) MDS cells, lenalidomide mediates CRBN-dependent ubiquitination and degradation of casein kinase I isoform alpha (CK1α).
“in del(5q) MDS cells, lenalidomide mediates the CRBN-dependent ubiquitination and degradation of casein kinase I isoform α (CK1α)15.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [15]
Lenalidomide has activity in del(5q) MDS by inducing degradation of CK1α, the protein product of the haploinsufficient gene CSNK1A1 located on the common deleted region of chromosome 5q, leading to activation of p53 and subsequent apoptosis.
“Lenalidomide has activity in this disease by inducing degradation of CK1α, the protein product of the haploinsufficient gene CSNK1A1 that is located on the common deleted region of chromosome 5q, leading to activation of p53 and subsequent apoptosis15,96.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [15]
Most known neosubstrate proteins have been identified through proteomic analyses of different cell lineages.
“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 [15]
Loss of p53 leads to resistance of mouse HSPCs to CK1α targeting with lenalidomide, a direct inhibitor or genetic knockdown.
“Accordingly, loss of p53 leads to resistance of mouse HSPCs to Ck1α targeting with either lenalidomide, a direct inhibitor or genetic knockdown (FIG. 3b)15,160.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [15]
Del(5q) MDS HSPCs are typically sensitive to lenalidomide-mediated depletion of CK1α, which activates p53-dependent cell death.
“Del(5q) MDS HSPCs are typically sensitive to lenalidomide-mediated depletion of CK1α, which activates p53-dependent cell death15,96.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [15]
When lenalidomide binds to CRBN, casein kinase 1a (Ck1α) is specifically ubiquitinated and degraded.
“Ebert and colleagues who previously identified Ikaros and Aiolos reported that when lenalidomide binds to CRBN, casein kinase 1a (Ck1α) is specifically ubiquitinated and degraded [30].”
From Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs (2016) · cites this paper as [30]
CRBN binds thalidomide in its substrate binding pocket, creating a new surface to recruit other proteins for ubiquitination and degradation, such as IKZF1, IKZF3, or CK1α.
“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 [71]
The clinical efficacy of IMiDs is driven at least in part by their capacity to induce CRBN-mediated degradation of neo-substrates.
“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 [15]
Haploinsufficient expression of CK1α sensitizes myelodysplastic syndrome cells with deletion of chromosome 5q to CRBN-mediated degradation of CK1α by lenalidomide in patients with MDS (5q).
“haploinsufficient expression of CK1α sensitizes myelodysplastic syndrome (MDS) cells with deletion of chromosome 5q (del(5q)) to the CRBN-mediated degradation of CK1α by lenalidomide in patients with MDS (5q)15;”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [15]
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT
Martin Bland, J., & Altman, D. (1986) · The Lancet · doi:10.1016/s0140-6736(86)90837-8 · Cited by 47,965 · see citing works
Beckett, A. H., Rowland, M., & TURNER, P. (1965) · The Lancet · doi:10.1016/s0140-6736(65)91037-8 · Cited by 16,917 · see citing works
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
Ong, S.-E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200025-mcp200 · Cited by 5,574 · see citing works
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 · see citing works
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Krönke, J., Udeshi, N. D., Narla, A., Grauman, P., Hurst, S. N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., et al. (2014) · Science · doi:10.1126/science.1244851 · Cited by 1,879 · see citing works
Self-citationThe Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins
Lu, G., Middleton, R. E., Sun, H., Naniong, M., Ott, C. J., Mitsiades, C. S., Wong, K.-K., Bradner, J. E., & Kaelin, W. G. (2014) · Science · doi:10.1126/science.1244917 · Cited by 1,583 · see citing works
Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion
List, A., Dewald, G., Bennett, J., Giagounidis, A., Raza, A., Feldman, E., Powell, B., Greenberg, P., Thomas, D., Stone, R., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061292 · Cited by 1,319 · see citing works
Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
Fischer, E. S., Böhm, K., Lydeard, J. R., Yang, H., Stadler, M. B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G. M., et al. (2014) · Nature · doi:10.1038/nature13527 · Cited by 1,141 · see citing works
Identification of RPS14 as a 5q- syndrome gene by RNA interference screen
Ebert, B. L., Pretz, J. L., Bosco, J., Chang, C. Y., Tamayo, P., Galili, N., Raza, A., Root, D. E., Attar, E. C., Ellis, S. R., et al. (2008) · Nature · doi:10.1038/nature06494 · Cited by 925 · see citing works
Self-citationEfficacy of Lenalidomide in Myelodysplastic Syndromes
List, A., Kurtin, S., Roe, D. J., Buresh, A., Mahadevan, D., Fuchs, D., Rimsza, L., Heaton, R., Knight, R., & Zeldis, J. B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa041668 · Cited by 880 · see citing works
Ribosomopathies: human disorders of ribosome dysfunction
Narla, A., & Ebert, B. L. (2010) · Blood · doi:10.1182/blood-2009-10-178129 · Cited by 806 · see citing works
Self-citationGandhi, A. K., Kang, J., Havens, C. G., Conklin, T., Ning, Y., Wu, L., Ito, T., Ando, H., Waldman, M. F., Thakurta, A., et al. (2014) · British Journal of Haematology · doi:10.1111/bjh.12708 · Cited by 619 · see citing works
Self-citationIntegrated proteomic analysis of post-translational modifications by serial enrichment
Mertins, P., Qiao, J., Patel, J., Udeshi, N. D., Clauser, K. R., Mani, D. R., Burgess, M. W., Gillette, M. A., Jaffe, J. D., & Carr, S. A. (2013) · Nature Methods · doi:10.1038/nmeth.2518 · Cited by 619 · see citing works
Self-citationIsobaric Labeling-Based Relative Quantification in Shotgun Proteomics
Rauniyar, N., & Yates, J. R. (2014) · Journal of Proteome Research · doi:10.1021/pr500880b · Cited by 597 · see citing works
Heckl, D., Kowalczyk, M. S., Yudovich, D., Belizaire, R., Puram, R. V., McConkey, M. E., Thielke, A., Aster, J. C., Regev, A., & Ebert, B. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2951 · Cited by 555 · see citing works
Self-citationChamberlain, P. P., Lopez-Girona, A., Miller, K., Carmel, G., Pagarigan, B., Chie-Leon, B., Rychak, E., Corral, L. G., Ren, Y. J., Wang, M., et al. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2874 · Cited by 531 · see citing works
Self-citationExploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma
Yang, Y., Shaffer, A. L., Emre, N. C. T., Ceribelli, M., Zhang, M., Wright, G. W., Xiao, W., Powell, J. I., Platig, J., Kohlhammer, H., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.024 · Cited by 524 · see citing works
Fenaux, P., Giagounidis, A. A. N., Selleslag, D., Beyne‐Rauzy, O., Mufti, G. J., Mittelman, M., Muus, P., Boekhorst, P. A. W. T., Sanz, G. F., del Cañizo, C., et al. (2011) · Blood · doi:10.1182/blood-2011-01-330126 · Cited by 488 · see citing works
<i>TP53</i> Mutations in Low-Risk Myelodysplastic Syndromes With del(5q) Predict Disease Progression
Jädersten, M., Saft, L., Smith, A., Kulasekararaj, A., Pomplun, S., Göhring, G., Hedlund, A., Hast, R., Schlegelberger, B., Porwit, A., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.8576 · Cited by 463 · see citing works
Quantitative Temporal Viromics: An Approach to Investigate Host-Pathogen Interaction
Weekes, M. P., Tomašec, P., Huttlin, E. L., Fielding, C. A., Nusinow, D. P., Stanton, R. J., Wang, E. C. Y., Aicheler, R., Murrell, I., Wilkinson, G. W. G., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.028 · Cited by 427 · see citing works
Large-scale identification of ubiquitination sites by mass spectrometry
Udeshi, N. D., Mertins, P., Svinkina, T., & Carr, S. A. (2013) · Nature Protocols · doi:10.1038/nprot.2013.120 · Cited by 299 · see citing works
Self-citationThe CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis
Knippschild, U., Krüger, M., Richter, J., Xu, P., García-Reyes, B., Peifer, C., Halekotte, J., Bakulev, V. A., & Bischof, J. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00096 · Cited by 276 · see citing works
Narrowing and genomic annotation of the commonly deleted region of the 5q− syndrome
Boultwood, J., Fidler, C., Strickson, A., Watkins, F., Gama, S., Kearney, L., Tosi, S., Kasprzyk, A., Cheng, J., Jaju, R. J., et al. (2002) · Blood · doi:10.1182/blood.v99.12.4638 · Cited by 264 · see citing works
Pellagatti, A., Jädersten, M., Forsblom, A., Cattan, H., Christensson, B., Emanuelsson, E. K., Merup, M., Nilsson, L., Samuelsson, J., Sander, B., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610477104 · Cited by 232 · see citing works
Cancer vulnerabilities unveiled by genomic loss
Nijhawan, D., Zack, T., Ren, Y., Strickland, M., Lamothe, R., Schumacher, S., Tsherniak, A., Besche, H. C., Rosenbluh, J., Shehata, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.07.023 · Cited by 224 · see citing works
Chesi, M., Matthews, G. M., Garbitt, V. M., Palmer, S. E., Shortt, J., Lefebure, M., Stewart, A. K., Johnstone, R. W., & Bergsagel, P. L. (2012) · Blood · doi:10.1182/blood-2012-02-412783 · Cited by 215 · see citing works
CKIα ablation highlights a critical role for p53 in invasiveness control
Elyada, E., Pribluda, A., Goldstein, R. E., Morgenstern, Y., Brachya, G., Cojocaru, G., Snir-Alkalay, I., Burstain, I., Haffner‐Krausz, R., Jung, S., et al. (2011) · Nature · doi:10.1038/nature09673 · Cited by 199 · see citing works
Sheng, W., Chen, X., Rocha, K., Epling‐Burnette, P. K., Djeu, J. Y., Liu, Q., Byrd, J. C., Sokol, L., Lawrence, N., Pireddu, R., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811267106 · Cited by 192 · see citing works
Role of Casein Kinase 1A1 in the Biology and Targeted Therapy of del(5q) MDS
Schneider, R. K., Ademà, V., Heckl, D., Järås, M., Mallo, M., Lord, A. M., Chu, L. P., McConkey, M. E., Kramann, R., Mullally, A., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.08.001 · Cited by 188 · see citing works
Self-citationTeratogenic effects of thalidomide in rabbits, rats, hamsters, and mice
Fratta, I., Sigg, E. B., & Maiorana, K. (1965) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(65)90095-5 · Cited by 155 · see citing works
Gene expression profiling of CD34+ cells in patients with the 5q− syndrome
Boultwood, J., Pellagatti, A., Cattan, H., Lawrie, C. H., Giagounidis, A. A. N., Malcovati, L., Porta, M. G. D., Jädersten, M., Killick, S. B., Fidler, C., et al. (2007) · British Journal of Haematology · doi:10.1111/j.1365-2141.2007.06833.x · Cited by 151 · see citing works
Casein kinase: the triple meaning of a misnomer
Venerando, A., Ruzzene, M., & Pinna, L. A. (2014) · Biochemical Journal · doi:10.1042/bj20140178 · Cited by 134 · see citing works
CK1α Plays a Central Role in Mediating MDM2 Control of p53 and E2F-1 Protein Stability
Huart, A.-S., MacLaine, N. J., Meek, D. W., & Hupp, T. R. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.052647 · Cited by 110 · see citing works
Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia
Järås, M., Miller, P. G., Chu, L. P., Puram, R. V., Fink, E. C., Schneider, R. K., Al-Shahrour, F., Peña, P., Breyfogle, L. J., Hartwell, K. A., et al. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20131033 · Cited by 92 · see citing works
Self-citationGraubert, T. A., Payton, M. A., Shao, J., Walgren, R. A., Monahan, R. S., Frater, J. L., Walshauser, M. A., Martin, M. G., Kasai, Y., & Walter, M. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004583 · Cited by 50 · see citing works
Casein Kinase 1α Regulates an MDMX Intramolecular Interaction To Stimulate p53 Binding
Wu, S., Chen, L., Becker, A., Schönbrunn, E., & Chen, J. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00851-12 · Cited by 48 · see citing works
Gene deletion: a new target for cancer chemotherapy
Frei, E. (1993) · The Lancet · doi:10.1016/0140-6736(93)91764-d · Cited by 19 · see citing works
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A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles
Subramanian, A., Narayan, R., Corsello, S. M., Peck, D. D., Natoli, T. E., Lu, X., Gould, J., Davis, J. F., Tubelli, A. A., Asiedu, J. K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.049 · Cited by 3,515 · see citing works
PROTAC targeted protein degraders: the past is prologue
Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395 · see citing works
Ubiquitin ligases: structure, function, and regulation
Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499 · see citing works
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486 · see citing works
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009 · see citing works
Targeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960 · see citing works
Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15
Han, T., Goralski, M., Gaskill, N., Capota, E., Kim, J., Ting, T. C., Xie, Y., Williams, N. S., & Nijhawan, D. (2017) · Science · doi:10.1126/science.aal3755 · Cited by 762 · see citing works
A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase
Matyskiela, M. E., Lu, G., Ito, T., Pagarigan, B., Lu, C.-C., Miller, K., Fang, W., Wang, N.-Y., Nguyen, D., Houston, J., et al. (2016) · Nature · doi:10.1038/nature18611 · Cited by 701 · see citing works
Self-citationA Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo
Bai, L., Zhou, H., Xu, R., Zhao, Y., Chinnaswamy, K., McEachern, D., Chen, J., Yang, C.-Y., Liu, Z., Wang, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.002 · Cited by 652 · see citing works
Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase
Petzold, G., Fischer, E. S., & Thomä, N. H. (2016) · Nature · doi:10.1038/nature16979 · Cited by 620 · see citing works
Plasticity in binding confers selectivity in ligand-induced protein degradation
Nowak, R. P., DeAngelo, S. L., Buckley, D., He, Z., Donovan, K. A., An, J., Safaee, N., Jedrychowski, M. P., Ponthier, C. M., Ishoey, M., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0055-y · Cited by 615 · see citing works
Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN
Sievers, Q. L., Petzold, G., Bunker, R. D., Renneville, A., Słabicki, M., Liddicoat, B. J., Abdulrahman, W., Mikkelsen, T., Ebert, B. L., & Thomä, N. H. (2018) · Science · doi:10.1126/science.aat0572 · Cited by 537 · see citing works
“which the b-hairpin zinc-coordinating cysteines are separated by two, three, or four residues [C-x(2,4)-C], but only C-x(2)-C ZFs were found destabilized in the screen (Fig.”
InfluentialSelf-citationDonovan, K. A., An, J., Nowak, R. P., Yuan, J. C., Fink, E. C., Berry, B. C., Ebert, B. L., & Fischer, E. S. (2018) · eLife · doi:10.7554/elife.38430 · Cited by 509 · see citing works
“IMiDs can also promote degradation of targets that lack a zinc finger domain, including Casein Kinase 1 alpha (CSNK1A1) (Krönke et al., 2015; Petzold et al., 2016) and GSPT1 (Matyskiela et al.”
BackgroundResultInfluentialSelf-citationDevelopment of targeted protein degradation therapeutics
Chamberlain, P. P., & Hamann, L. G. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0362-y · Cited by 489 · see citing works
Self-citationA small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment
Hyer, M. L., Milhollen, M. A., Ciavarri, J., Fleming, P., Traore, T., Sappal, D., Huck, J., Shi, J., Gavin, J., Brownell, J., et al. (2018) · Nature Medicine · doi:10.1038/nm.4474 · Cited by 447 · see citing works
A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader
Huang, H.-T., Dobrovolsky, D., Paulk, J., Yang, G., Weisberg, E. L., Doctor, Z. M., Buckley, D. L., Cho, J.-H., Ko, E., Jang, J., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.10.005 · Cited by 437 · see citing works
Harnessing the anti-cancer natural product nimbolide for targeted protein degradation
Spradlin, J. N., Hu, X., Ward, C. C., Brittain, S. M., Jones, M. D., Ou, L., To, M., Proudfoot, A., Ornelas, E., Woldegiorgis, M., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0304-8 · Cited by 432 · see citing works
Selective degradation of splicing factor CAPERα by anticancer sulfonamides
Uehara, T., Minoshima, Y., Sagane, K., Sugi, N. H., Mitsuhashi, K. O., Yamamoto, N., Kamiyama, H., Takahashi, K., Kotake, Y., Uesugi, M., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2363 · Cited by 396 · see citing works
Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery
Dong, G., Ding, Y., He, S., & Sheng, C. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00895 · Cited by 369 · see citing works
SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate
Matyskiela, M. E., Couto, S., Zheng, X., Lu, G., Hui, J., Stamp, K., Drew, C., Ren, Y., Wang, M., Carpenter, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0129-x · Cited by 338 · see citing works
Self-citationTargeting an RNA-Binding Protein Network in Acute Myeloid Leukemia
Wang, E., Lu, S. X., Pastore, A., Chen, X., Imig, J., Chun-Wei Lee, S., Hockemeyer, K., Ghebrechristos, Y. E., Yoshimi, A., Inoue, D., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.01.010 · Cited by 338 · see citing works
A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos
Matyskiela, M. E., Zhang, W., Man, H.-W., Muller, G., Khambatta, G., Baculi, F., Hickman, M., LeBrun, L., Pagarigan, B., Carmel, G., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01921 · Cited by 309 · see citing works
Self-citationWaste disposal—An attractive strategy for cancer therapy
Salami, J., & Crews, C. M. (2017) · Science · doi:10.1126/science.aam7340 · Cited by 279 · see citing works
Small-molecule-induced polymerization triggers degradation of BCL6
Słabicki, M., Yoon, H., Koeppel, J., Nitsch, L., Roy Burman, S. S., Di Genua, C., Donovan, K. A., Sperling, A. S., Hunkeler, M., Tsai, J. M., et al. (2020) · Nature · doi:10.1038/s41586-020-2925-1 · Cited by 270 · see citing works
Self-citationSchneider, M., Radoux, C. J., Hercules, A., Ochoa, D., Dunham, I., Zalmas, L.-P., Hessler, G., Ruf, S., Shanmugasundaram, V., Hann, M. M., et al. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00245-x · Cited by 273 · see citing works
Specific Knockdown of Endogenous Tau Protein by Peptide-Directed Ubiquitin-Proteasome Degradation
Chu, T.-T., Gao, N., Li, Q.-Q., Chen, P.-G., Yang, X.-F., Chen, Y.-X., Zhao, Y.-F., & Li, Y.-M. (2016) · Cell Chemical Biology · doi:10.1016/j.chembiol.2016.02.016 · Cited by 247 · see citing works
Sekeres, M. A., Othus, M., List, A. F., Odenike, O., Stone, R. M., Gore, S. D., Litzow, M. R., Buckstein, R., Fang, M., Roulston, D., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2015.66.2510 · Cited by 237 · see citing works
Hughes, S. J., & Ciulli, A. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170041 · Cited by 240 · see citing works
PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery
Gu, S., Cui, D., Chen, X., Xiong, X., & Zhao, Y. (2018) · BioEssays · doi:10.1002/bies.201700247 · Cited by 231 · see citing works
Surka, C., Jin, L., Mbong, N., Lu, C.-C., Jang, I. S., Rychak, E., Mendy, D., Clayton, T., Tindall, E., Hsu, C., et al. (2021) · Blood · doi:10.1182/blood.2020008676 · Cited by 229 · see citing works
Self-citationTargeted protein degradation via intramolecular bivalent glues
Hsia, O., Hinterndorfer, M., Cowan, A. D., Iso, K., Ishida, T., Sundaramoorthy, R., Nakasone, M. A., Imrichova, H., Schätz, C., Rukavina, A., et al. (2024) · Nature · doi:10.1038/s41586-024-07089-6 · Cited by 222 · see citing works
The novel mechanism of lenalidomide activity
Fink, E. C., & Ebert, B. L. (2015) · Blood · doi:10.1182/blood-2015-07-567958 · Cited by 213 · see citing works
Self-citationTargeted Protein Degradation by Small Molecules
Bondeson, D. P., & Crews, C. M. (2017) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103507 · Cited by 207 · see citing works
The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron
Ichikawa, S., Flaxman, H. A., Xu, W., Vallavoju, N., Lloyd, H. C., Wang, B., Shen, D., Pratt, M. R., & Woo, C. M. (2022) · Nature · doi:10.1038/s41586-022-05333-5 · Cited by 195 · see citing works
Chasing molecular glue degraders: screening approaches
Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C., & Mayor-Ruiz, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00197g · Cited by 200 · see citing works
Yang, J., Li, Y., Aguilar, A., Liu, Z., Yang, C.-Y., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00846 · Cited by 190 · see citing works
pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase
An, J., Ponthier, C. M., Sack, R., Seebacher, J., Stadler, M. B., Donovan, K. A., & Fischer, E. S. (2017) · Nature Communications · doi:10.1038/ncomms15398 · Cited by 176 · see citing works
Eichner, R., Heider, M., Fernández-Sáiz, V., van Bebber, F., Garz, A.-K., Lemeer, S., Rudelius, M., Targosz, B.-S., Jacobs, L., Knorn, A.-M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4128 · Cited by 183 · see citing works
Van Nguyen, T., Lee, J. E., Sweredoski, M. J., Yang, S.-J., Jeon, S.-J., Harrison, J. S., Yim, J.-H., Lee, S. G., Handa, H., Kuhlman, B., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.032 · Cited by 177 · see citing works
“Recent studies have revealed that binding of IMiDs to CRBN promotes recruitment of neosubstrates, including Ikaros (IKZF1), Aiolos (IKZF3) (Kronke et al., 2014; Lu et al., 2014) and casein kinase 1A1 (CK1α) (Kronke et al., 2015) to CRL4CRBN, leading to their increased ubiquitylation and proteasome-dependent degradatio…”
BackgroundInfluentialHarnessing the Power of Proteolysis for Targeted Protein Inactivation
Verma, R., Mohl, D., & Deshaies, R. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.01.010 · Cited by 185 · see citing works
From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation
Oleinikovas, V., Gainza, P., Ryckmans, T., Fasching, B., & Thomä, N. H. (2024) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-022123-104147 · Cited by 178 · see citing works
Ishoey, M., Chorn, S., Singh, N., Jaeger, M. G., Brand, M., Paulk, J., Bauer, S., Erb, M. A., Parapatics, K., Müller, A. C., et al. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b00969 · Cited by 177 · see citing works
Discovery and characterization of a selective IKZF2 glue degrader for cancer immunotherapy
Bonazzi, S., d’Hennezel, E., Beckwith, R. E. J., Xu, L., Fazal, A., Magracheva, A., Ramesh, R., Cernijenko, A., Antonakos, B., Bhang, H.-E. C., et al. (2023) · Cell Chemical Biology · doi:10.1016/j.chembiol.2023.02.005 · Cited by 167 · see citing works
Haven't got a glue: Protein surface variation for the design of molecular glue degraders
Kozicka, Z., & Thomä, N. H. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2021.04.009 · Cited by 170 · see citing works
Steinebach, C., Ng, Y. L. D., Sosič, I., Lee, C.-S., Chen, S., Lindner, S., Vu, L. P., Bricelj, A., Haschemi, R., Monschke, M., et al. (2020) · Chemical Science · doi:10.1039/d0sc00167h · Cited by 148 · see citing works
Self-citationCancer therapies based on targeted protein degradation — lessons learned with lenalidomide
Jan, M., Sperling, A. S., & Ebert, B. L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00479-z · Cited by 137 · see citing works
Self-citationp63 is a cereblon substrate involved in thalidomide teratogenicity
Asatsuma-Okumura, T., Ando, H., De Simone, M., Yamamoto, J., Sato, T., Shimizu, N., Asakawa, K., Yamaguchi, Y., Ito, T., Guerrini, L., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0366-7 · Cited by 134 · see citing works
Defining molecular glues with a dual-nanobody cannabidiol sensor
Cao, S., Kang, S., Mao, H., Yao, J., Gu, L., & Zheng, N. (2022) · Nature Communications · doi:10.1038/s41467-022-28507-1 · Cited by 125 · see citing works
Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice
Fink, E. C., McConkey, M., Adams, D. N., Haldar, S. D., Kennedy, J. A., Guirguis, A. A., Udeshi, N. D., Mani, D. R., Chen, M., Liddicoat, B., et al. (2018) · Blood · doi:10.1182/blood-2018-05-852798 · Cited by 131 · see citing works
Self-citationLigandability of E3 Ligases for Targeted Protein Degradation Applications
Belcher, B. P., Ward, C. C., & Nomura, D. K. (2023) · Biochemistry · doi:10.1021/acs.biochem.1c00464 · Cited by 132 · see citing works
Casein kinase 1α: biological mechanisms and theranostic potential
Jiang, S., Zhang, M., Sun, J., & Yang, X. (2018) · Cell Communication and Signaling · doi:10.1186/s12964-018-0236-z · Cited by 130 · see citing works
Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15
Ting, T. C., Goralski, M., Klein, K., Wang, B., Kim, J., Xie, Y., & Nijhawan, D. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.079 · Cited by 123 · see citing works
Sievers, Q. L., Gasser, J. A., Cowley, G. S., Fischer, E. S., & Ebert, B. L. (2018) · Blood · doi:10.1182/blood-2018-01-821769 · Cited by 124 · see citing works
Self-citationAcute pharmacological degradation of Helios destabilizes regulatory T cells
Wang, E. S., Verano, A. L., Nowak, R. P., Yuan, J. C., Donovan, K. A., Eleuteri, N. A., Yue, H., Ngo, K. H., Lizotte, P. H., Gokhale, P. C., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00802-w · Cited by 124 · see citing works
Fetal haemoglobin in sickle-cell disease: from genetic epidemiology to new therapeutic strategies
Lettre, G., & Bauer, D. E. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01341-0 · Cited by 104 · see citing works
Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex
Matyskiela, M. E., Clayton, T., Zheng, X., Mayne, C., Tran, E., Carpenter, A., Pagarigan, B., McDonald, J., Rolfe, M., Hamann, L. G., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0405-9 · Cited by 103 · see citing works
Self-citationCereblon modulators: Low molecular weight inducers of protein degradation
Chamberlain, P. P., & Cathers, B. E. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2019.02.004 · Cited by 106 · see citing works
Self-citationBifunctional chemical probes inducing protein–protein interactions
Maniaci, C., & Ciulli, A. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.07.003 · Cited by 100 · see citing works
Novel immunomodulatory drugs and neo-substrates
Gao, S., Wang, S., & Song, Y. (2020) · Biomarker Research · doi:10.1186/s40364-020-0182-y · Cited by 95 · see citing works
Mining the CRBN target space redefines rules for molecular glue-induced neosubstrate recognition
Petzold, G., Gainza, P., Annunziato, S., Lamberto, I., Trenh, P., McAllister, L. A., DeMarco, B., Schwander, L., Bunker, R. D., Zlotosch, M., et al. (2025) · Science · doi:10.1126/science.adt6736 · Cited by 117 · see citing works
Advances in targeted degradation of endogenous proteins
Röth, S., Fulcher, L. J., & Sapkota, G. P. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03112-6 · Cited by 92 · see citing works
Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide
Furihata, H., Yamanaka, S., Honda, T., Miyauchi, Y., Asano, A., Shibata, N., Tanokura, M., Sawasaki, T., & Miyakawa, T. (2020) · Nature Communications · doi:10.1038/s41467-020-18488-4 · Cited by 89 · see citing works
p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates
Nguyen, T. V., Li, J., Lu, C.-C. (., Mamrosh, J. L., Lu, G., Cathers, B. E., & Deshaies, R. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700949114 · Cited by 85 · see citing works
Self-citationCereblon and its downstream substrates as molecular targets of immunomodulatory drugs
Ito, T., & Handa, H. (2016) · International Journal of Hematology · doi:10.1007/s12185-016-2073-4 · Cited by 84 · see citing works
Liu, J., Song, T., Zhou, W., Xing, L., Wang, S., Ho, M., Peng, Z., Tai, Y.-T., Hideshima, T., Anderson, K. C., et al. (2019) · Leukemia · doi:10.1038/s41375-018-0205-y · Cited by 83 · see citing works
Fang, J., Liu, X., Bolanos, L., Barker, B., Rigolino, C., Cortelezzi, A., Oliva, E. N., Cuzzola, M., Grimes, H. L., Fontanillo, C., et al. (2016) · Nature Medicine · doi:10.1038/nm.4127 · Cited by 83 · see citing works
Self-citationUBE2G1 governs the destruction of cereblon neomorphic substrates
Lu, G., Weng, S., Matyskiela, M., Zheng, X., Fang, W., Wood, S., Surka, C., Mizukoshi, R., Lu, C.-C., Mendy, D., et al. (2018) · eLife · doi:10.7554/elife.40958 · Cited by 78 · see citing works
Self-citationBai, N., Riching, K. M., Makaju, A., Wu, H., Acker, T. M., Ou, S.-C., Zhang, Y., Shen, X., Bulloch, D. N., Rui, H., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101653 · Cited by 77 · see citing works
Torres, S. E., Gallagher, C. M., Plate, L., Gupta, M., Liem, C. R., Guo, X., Tian, R., Stroud, R. M., Kampmann, M., Weissman, J. S., et al. (2019) · eLife · doi:10.7554/elife.46595 · Cited by 76 · see citing works
Current and emerging strategies for management of myelodysplastic syndromes
Saygin, C., & Carraway, H. E. (2021) · Blood Reviews · doi:10.1016/j.blre.2020.100791 · Cited by 70 · see citing works
Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries
Wang, B., Liu, J., Tandon, I., Wu, S., Teng, P., Liao, J., & Tang, W. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113425 · Cited by 67 · see citing works
Monomeric Targeted Protein Degraders
Hanan, E. J., Liang, J., Wang, X., Blake, R. A., Blaquiere, N., & Staben, S. T. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00093 · Cited by 69 · see citing works
Development of PDE6D and CK1α Degraders through Chemical Derivatization of FPFT-2216
Teng, M., Lu, W., Donovan, K. A., Sun, J., Krupnick, N. M., Nowak, R. P., Li, Y.-D., Sperling, A. S., Zhang, T., Ebert, B. L., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01832 · Cited by 63 · see citing works
Self-citationHydrophobic tagging-mediated degradation of Alzheimer's disease related Tau
Gao, N., Chu, T.-T., Li, Q.-Q., Lim, Y.-J., Qiu, T., Ma, M.-R., Hu, Z.-W., Yang, X.-F., Chen, Y.-X., Zhao, Y.-F., et al. (2017) · RSC Advances · doi:10.1039/c7ra05347a · Cited by 62 · see citing works
Profiling the Landscape of Drug Resistance Mutations in Neosubstrates to Molecular Glue Degraders
Gosavi, P. M., Ngan, K. C., Yeo, M. J. R., Su, C., Li, J., Lue, N. Z., Hoenig, S. M., & Liau, B. B. (2022) · ACS Central Science · doi:10.1021/acscentsci.1c01603 · Cited by 56 · see citing works
Chen, H., Chen, F., Liu, N., Wang, X., & Gou, S. (2018) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2018.09.005 · Cited by 51 · see citing works
A critical evaluation of the approaches to targeted protein degradation for drug discovery
Chopra, R., Sadok, A., & Collins, I. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2019.02.002 · Cited by 53 · see citing works
Self-citationA decade of progress in myelodysplastic syndrome with chromosome 5q deletion
List, A., Ebert, B. L., & Fenaux, P. (2018) · Leukemia · doi:10.1038/s41375-018-0029-9 · Cited by 49 · see citing works
Self-citationShen, C., Nayak, A., Neitzel, L. R., Adams, A. A., Silver-Isenstadt, M., Sawyer, L. M., Benchabane, H., Wang, H., Bunnag, N., Li, B., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25634-z · Cited by 43 · see citing works
Bellail, A. C., Jin, H. R., Lo, H.-Y., Jung, S. H., Hamdouchi, C., Kim, D., Higgins, R. K., Blanck, M., le Sage, C., Cross, B. C. S., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abh1486 · Cited by 42 · see citing works
Martinez-Høyer, S., Deng, Y., Parker, J., Jiang, J., Mo, A., Docking, T. R., Gharaee, N., Li, J., Umlandt, P., Fuller, M., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0497-9 · Cited by 42 · see citing works
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 · see citing works
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 · see citing works
Patil, A., Manzano, M., & Gottwein, E. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019031732 · Cited by 29 · see citing works
CK1α overexpression correlates with poor survival in colorectal cancer
Richter, J., Kretz, A.-L., Lemke, J., Fauler, M., Werner, J.-U., Paschke, S., Leithäuser, F., Henne-Bruns, D., Hillenbrand, A., & Knippschild, U. (2018) · BMC Cancer · doi:10.1186/s12885-018-4019-0 · Cited by 28 · see citing works
Selective and Potent Molecular Glue Degraders for NIMA‐Related Kinase 7
Chen, L., Huang, L., Wen, W., Zeng, P., Wu, Y., Han, Q., Chen, X., Guo, Z., Yu, H., Lu, W., et al. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202500169 · Cited by 24 · see citing works
DeAngelo, D. J., Brunner, A. M., Werner, L., Avigan, D., Fathi, A. T., Sperling, A. S., Washington, A., Stroopinsky, D., Rosenblatt, J., McMasters, M., et al. (2018) · American Journal of Hematology · doi:10.1002/ajh.24968 · Cited by 16 · see citing works
Self-citationIdentification of an allosteric site on the E3 ligase adapter cereblon
Dippon, V. N., Rizvi, Z., Choudhry, A. E., Chung, C.-W., Alkuraya, I. F., Xu, W., Tao, X. B., Jurewicz, A. J., Schneck, J. L., Chen, W., et al. (2026) · Nature · doi:10.1038/s41586-025-09994-w · Cited by 14 · see citing works
From serendipity to strategy: molecular glue degraders in cancer therapeutics
Darling, S., Bajrami, I., & West, S. C. (2025) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2025.2564068 · Cited by 10 · see citing works
“…and leads to clonal arrest of the 5q-deleted population which ultimately drives disease regression (wei et al. 2009; Schneider et al. 2014; Krönke et al. 2015). while cK1α plays a multifaceted role in the cell it is thought that its direct phosphorylation of MDM2 contributes to 5q-MDS…”
Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry
Annunziato, S., Quan, C., Donckele, E. J., Lamberto, I., Bunker, R. D., Zlotosch, M., Schwander, L., Murthy, A., Wiedmer, L., Staehly, C., et al. (2026) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01738-8 · Cited by 9 · see citing works
“Cereblon (CRBN), for example, serves as the substrate receptor of the CRL4 CRBN E3 ubiquitin ligase, a multisubunit Cullin– RING ligase (CRL) complex that is repurposed by lenalidomide-type MGDs in the treatment of hematologic malignancies 5–9 .”
Casein Kinase 1α—A Target for Prostate Cancer Therapy?
Lishman-Walker, E., & Coffey, K. (2024) · Cancers · doi:10.3390/cancers16132436 · Cited by 4 · see citing works
- Authors
- Krönke, J., Fink, E. C., Hollenbach, P. W., MacBeth, K. J., Hurst, S. N., Udeshi, N. D., Chamberlain, P. P., Mani, D. R., Man, H. W., Gandhi, A. K., Svinkina, T., Schneider, R. K., McConkey, M., Järås, M., Griffiths, E., Wetzler, M., Bullinger, L., Cathers, B. E., Carr, S. A., Chopra, R., & Ebert, B. L.
- Affiliations
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Roswell Park Comprehensive Cancer Center (US)
- University Hospital Ulm (DE)
- Corresponding author
- Ebert, Benjamin L.
- ORCID
- Venue
- Nature
- Published
- 2015-07
- Volume
- 523
- Issue
- 7559
- Pages
- 183-188
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4853910
- OpenAlex
- W1527383154
- Cited by
- 863
- References
- 39
- Citations by year
- 2026: 71 · 2025: 95 · 2024: 92 · 2023: 59 · 2022: 87 · 2021: 100 · 2020: 85 · 2019: 69 · 2018: 81 · 2017: 65 · 2016: 49 · 2015: 10
- FWCI
- 29.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Cancer Research UK (11566)
- National Heart, Lung, and Blood Institute (R01HL082945)
- National Cancer Institute (P01CA108631, P01CA066996)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- lenalidomide, del(5q) myelodysplastic syndrome, CK1α, E3 ubiquitin ligase, ubiquitination, protein degradation, cereblon, thalidomide derivatives, haploinsufficiency, drug resistance, thalidomide
- MeSH terms
- Lenalidomide, Amino Acid Sequence, Animals, Cell Line, Gene Expression Regulation, Humans, Immunologic Factors, Molecular Sequence Data, Myelodysplastic Syndromes, Peptide Hydrolases, Species Specificity, Thalidomide, Sequence Alignment, Sequence Deletion, Jurkat Cells, K562 Cells, Ubiquitin-Protein Ligases, Casein Kinase I, Mice, Ubiquitination, HEK293 Cells, Proteolysis
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