The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
Open accessAbstract
In the 1950s, the drug thalidomide, administered as a sedative to pregnant women, led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-associated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4(CRBN). Here we present crystal structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs. Using an unbiased screen, we identified the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4(CRBN). Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
“These residues form a small hydrophobic pocket (tri-Trp pocket), which shows 100% conservation in CRBN orthologs across animal and plant kingdoms (Chamberlain et al., 2014; Fischer et al., 2014) (Figure S7A).”
From Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon (2016) · cites this paper as Fischer 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
“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 [7]
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 [7]
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
“Previous work has implicated the second C2H2 ZF domain in IKZF1 and IKZF3 (5, 7), and ZF4 of ZFP91 as the drug-inducible degrons (5, 7, 16).”
From Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN (2018) · cites this paper as [7]
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
“Given the CRL4CRBN protein architecture and its ~100 Å ubiquitination radius (6, 7, 22)”
From Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN (2018) · cites this paper as [7]
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
“the second breakthrough came in 2014 when a series of landmark studies revealed that thalidomide, and its more potent derivative lenalidomide, did not behave as inhibitors but in fact functioned as molecular glue degraders analogous to the auxin degrader tiR1 (chamberlain et al. 2014;Fischer et al. 2014;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 Fischer et al. 2014
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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 [12]
The cited source says what the claim attributes to it.
In the citing paper
“The CTD harbors the IMiD binding pocket formed by Trp380, Trp386 and Trp400, with a phenylalanine residue at the base (Phe402) (Chamberlain et al., 2014; Fischer et al., 2014).”
From Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon (2016) · cites this paper as Fischer et al., 2014
The cited source says what the claim attributes to it.
In the citing paper
“orthogonally confirmed dose-dependent KAT2A degradation by western blot, and demonstrated that this degradation can be rescued by pre-treatment with a UBA3/NAE1 inhibitor, MLN4924 (37), a proteasome inhibitor, bortezomib (38), and a competing CRBN ligand, pomalidomide (7) (Fig. 1D).”
From Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues (2026) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Structural studies show that cul4 can rotate up to 150° around DDB1, the cRBN adaptor, generating a large ubiquitylation zone spacious enough to allow cRBN autoubiquitylation without a substrate being present (Zimmerman et al. 2010;Fischer et al. 2014).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Fischer et al. 2014
In the citing paper
“Previous studies have shown that IMiDs can occupy a tryptophan cage binding site on CRBN with an affinity of ~150–250 nM35.”
From Defining molecular glues with a dual-nanobody cannabidiol sensor (2022) · cites this paper as [35]
In the citing paper
“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 [25]
In the citing paper
“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 [25]
In the citing paper
“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 [25]
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 [7]
In the citing paper
“All pharmacologically active derivatives of thalidomide contain a glutarimide ring that directly binds within a conserved pocket on the surface of CRBN17”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [17]
In the citing paper
“Each target protein has been found to contain a structural degron composed of a β-hairpin with a pinnacle glycine motif, most often in the form of a Cys2-His2 (C2H2) zinc finger domain, that binds to a composite thalidomide analogue–CRBN surface17,117,121,167.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [17]
In the citing paper
“Both groups concluded that IMiDs, via their glutarimide moiety, become inserted into the tripletryptophan (tri-Trp) pocket composed of three tryptophan residues (W380, W386, and W400) located at the C-teminus of CRBN.”
From Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs (2016) · cites this paper as [33]
In the citing paper
“However, thalidomide displaces endogenous CRBN substrates, such as the transcription factor MEIS2 which is involved in embryonic development, perhaps explaining its teratogenic effects in pregnant women [69, 73–75].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [69]
In the citing paper
“CRBN is a substrate recognition unit of the CUL4–RBX1–DDB1 E3 ligase complex [69].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [69]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Antitumor Activity of Thalidomide in Refractory Multiple Myeloma
Singhal, S., Mehta, J., Desikan, R., Ayers, D., Roberson, P., Eddlemon, P., Munshi, N., Anaissie, E., Wilson, C., Dhodapkar, M., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199911183412102 · Cited by 2,575
Thalidomide is an inhibitor of angiogenesis.
D'Amato, R. J., Loughnan, M. S., Flynn, E., & Folkman, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.4082 · Cited by 2,454
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278
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
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
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
Hornbeck, P. V., Kornhauser, J. M., Tkachev, S., Zhang, B., Skrzypek, E., Murray, B. W., Latham, V. M., & Sullivan, M. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1122 · Cited by 1,636
The 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
ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures
Landau, M., Mayrose, I., Rosenberg, Y., Glaser, F., Martz, E., Pupko, T., & Ben‐Tal, N. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki370 · Cited by 1,379
THALIDOMIDE AND CONGENITAL ABNORMALITIES
Mcbride, W. G. (1961) · The Lancet · doi:10.1016/s0140-6736(61)90927-8 · Cited by 1,141
The evolution of thalidomide and its IMiD derivatives as anticancer agents
Bartlett, J. B., Dredge, K. S., & Dalgleish, A. G. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1323 · Cited by 817
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
Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complex
Kissinger, C. R., Parge, H. E., Knighton, D. R., Lewis, C. T., Pelletier, L. A., Tempczyk, A., Kalish, V. J., Tucker, K. D., Showalter, R. E., Moomaw, E. W., et al. (1995) · Nature · doi:10.1038/378641a0 · Cited by 768
Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery
Angers, S., Li, T., Yi, X., MacCoss, M. J., Moon, R. T., & Zheng, N. (2006) · Nature · doi:10.1038/nature05175 · Cited by 674
Mechanisms and function of substrate recruitment by F-box proteins
Skaar, J. R., Pagan, J. K., & Pagano, M. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3582 · Cited by 671
Jin, J., Arias, E. E., Chen, J., Harper, J. W., & Walter, J. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.08.010 · Cited by 632
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
Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide
Zhu, Y. X., Braggio, E., Shi, C.-X., Bruins, L. A., Schmidt, J. E., Van Wier, S., Chang, X.-B., Bjorklund, C. C., Fonseca, R., Bergsagel, P. L., et al. (2011) · Blood · doi:10.1182/blood-2011-05-356063 · Cited by 607
Thalidomide in the treatment of lepra reactions
Sheskin, J. (1965) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt196563303 · Cited by 534
The Molecular Basis of CRL4DDB2/CSA Ubiquitin Ligase Architecture, Targeting, and Activation
Fischer, E. S., Scrima, A., Böhm, K., Matsumoto, S., Lingaraju, G. M., Faty, M., Yasuda, T., Cavadini, S., Wakasugi, M., Hanaoka, F., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.035 · Cited by 460
Self-citationStructural Basis of UV DNA-Damage Recognition by the DDB1–DDB2 Complex
Scrima, A., Koníčková, R., Czyzewski, B. K., Kawasaki, Y., Jeffrey, P. D., Groisman, R., Nakatani, Y., Iwai, S., Pavletich, N. P., & Thomä, N. H. (2008) · Cell · doi:10.1016/j.cell.2008.10.045 · Cited by 441
Self-citationTHALIDOMIDE AND CONGENITAL ABNORMALITIES
Lenz, W., Pfeiffer, R. A., Kosenow, W., & Hayman, D. J. (1962) · The Lancet · doi:10.1016/s0140-6736(62)92665-x · Cited by 418
Dynamics of Cullin-RING Ubiquitin Ligase Network Revealed by Systematic Quantitative Proteomics
Bennett, E. J., Rush, A. J., Gygi, S. P., & Harper, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.11.017 · Cited by 388
Self-citationPaige, S. L., Thomas, S., Stoick-Cooper, C. L., Wang, H., Maves, L., Sandstrom, R. S., Pabon, L., Reinecke, H., Pratt, G. A., Keller, G. M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.027 · Cited by 332
THALIDOMIDE AND CONGENITAL ABNORMALITIES
Burley, D. M., & Lenz, W. (1962) · The Lancet · doi:10.1016/s0140-6736(62)91217-5 · Cited by 324
Capdevila, J., Tsukui, T., Esteban, C. R., Zappavigna, V., & Belmonte, J. C. I. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80393-7 · Cited by 320
Huai, Q., Kim, H.-Y., Liu, Y., Zhao, Y., Mondragon, A., Liu, J. O., & Ke, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192206699 · Cited by 278
Li, T., Chen, X., Garbutt, K. C., Zhou, P., & Zheng, N. (2006) · Cell · doi:10.1016/j.cell.2005.10.033 · Cited by 259
A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation
Higgins, J. J., Pucilowska, J., Lombardi, R. Q., & Rooney, J. P. (2004) · Neurology · doi:10.1212/01.wnl.0000146196.01316.a2 · Cited by 250
Melchert, M., & List, A. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.01.022 · Cited by 246
Scrima, A., Fischer, E. S., Iwai, S., Gut, H., & Thomä, N. H. (2011) · Worldwide Protein Data Bank · doi:10.2210/pdb4a08/pdb · Cited by 233
Self-citationLi, T., Robert, E. I., Breugel, P. C. V., Strubin, M., & Zheng, N. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1719 · Cited by 223
Zhang, X., Horibata, K., Saijo, M., Ishigami, C., Ukai, A., Kanno, S.-I., Tahara, H., Neilan, E. G., Honma, M., Nohmi, T., et al. (2012) · Nature Genetics · doi:10.1038/ng.2228 · Cited by 201
Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy
Shortt, J., Hsu, A. K., & Johnstone, R. W. (2013) · Oncogene · doi:10.1038/onc.2012.599 · Cited by 103
Hofmeister, C. C., Yang, X., Pichiorri, F., Chen, P., Rozewski, D. M., Johnson, A. J., Lee, S., Liu, Z., Garr, C., Hade, E. M., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.4962 · Cited by 85
The application and biology of immunomodulatory drugs (IMiDs) in cancer
Pan, B., & Lentzsch, S. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.07.004 · Cited by 76
Detecting UV‐lesions in the genome: The modular CRL4 ubiquitin ligase does it best!
Scrima, A., Fischer, E. S., Lingaraju, G. M., Böhm, K., Cavadini, S., & Thomä, N. H. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.04.064 · Cited by 66
Self-citationIsosteric analogs of lenalidomide and pomalidomide: Synthesis and biological activity
Ruchelman, A. L., Man, H., Zhang, W., Chen, R., Capone, L., Kang, J., Parton, A., Corral, L. G., Schafer, P. H., Babusis, D. M., et al. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.10.071 · Cited by 61
The deubiquitinating protein USP24 interacts with DDB2 and regulates DDB2 stability
Zhang, L., Lubin, A., Chen, H., Sun, Z., & Gong, F. (2012) · Cell Cycle · doi:10.4161/cc.22688 · Cited by 52
Crowley, M. A., Conlin, L. K., Zackai, E. H., et al. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33375 · Cited by 50
A Mental Retardation-linked Nonsense Mutation in Cereblon Is Rescued by Proteasome Inhibition
Xu, G., Jiang, X., & Jaffrey, S. R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.472092 · Cited by 45
Hur, S., Stroud, R. M., & Finer-Moore, J. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600034200 · Cited by 37
Transport of thalidomide by the human intestinal Caco-2 monolayers
Zhou, S., Li, Y., Kestell, P., Schafer, P. H., Chan, E., & Paxton, J. W. (2005) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/bf03226408 · Cited by 17
Roche, S., Sewell, L., Meiller, J., et al. (2012) · Journal of Chromatography B · doi:10.1016/j.jchromb.2012.06.008 · Cited by 13
Research works printed but not linked: 1
- Li, T., Robert, E. I., van Breugel, P. C., Strubin, M. & Zheng, N. A promiscuous α-helical motif anchors viral hijackers and substrate receptors to the CUL4–DDB1 ubiquitin ligase machinery. Nature Struct. Mol. Biol. 17, 105–111 (2010) · DOI
Cited by
Sorted by citations
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
Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760
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
Structural basis of PROTAC cooperative recognition for selective protein degradation
Gadd, M. S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D. J., Zengerle, M., & Ciulli, A. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2329 · Cited by 1,242
Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
Lu, J., Qian, Y., Altieri, M., Dong, H., Wang, J., Raina, K., Hines, J., Winkler, J. D., Crew, A. P., Coleman, K., et al. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.05.009 · Cited by 1,140
Metadata
- Authors
- Fischer, E. S., Böhm, K., Lydeard, J. R., Yang, H., Stadler, M. B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G. M., Tichkule, R. B., Schebesta, M., Forrester, W. C., Schirle, M., Hassiepen, U., Ottl, J., Hild, M., Beckwith, R. E. J., Harper, J. W., Jenkins, J. L., & Thomä, N. H.
- Affiliations
- University of Basel (CH)
- Harvard University (US)
- Novartis (Switzerland) (CH)
- Corresponding author
- Thomä, Nicolas H.
- ORCID
- Venue
- Nature
- Published
- 2014-07-16
- Volume
- 512
- Issue
- 7512
- Pages
- 49-53
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4423819
- OpenAlex
- W2161413435
- Cited by
- 1,141
- References
- 44
- Citations by year
- 2026: 130 · 2025: 159 · 2024: 130 · 2023: 103 · 2022: 119 · 2021: 98 · 2020: 109 · 2019: 76 · 2018: 63 · 2017: 52 · 2016: 54 · 2015: 35 · 2014: 12
- FWCI
- 21.03
- 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)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Funders
- National Institute on Aging (AG011085, R01AG011085)
- 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 › Multiple Myeloma Research and Treatments
- Keywords
- thalidomide, lenalidomide, pomalidomide, immunomodulators, E3 ubiquitin ligase, enantioselective binding, MEIS2, IKZF1, IKZF3, multiple myeloma
- MeSH terms
- Lenalidomide, DNA-Binding Proteins, Humans, Models, Molecular, Peptide Hydrolases, Protein Binding, Structure-Activity Relationship, Substrate Specificity, Thalidomide, Transcription Factors, Crystallography, X-Ray, Homeodomain Proteins, Ubiquitin-Protein Ligases, Multiprotein Complexes, Adaptor Proteins, Signal Transducing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
