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Currently, you can access the following clinical trials being conducted worldwide:

351,441 studies
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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 10/22/2020.
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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 10/22/2020.
  • Cereblon/E3 Ligase Pathway

    The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

     

    Cereblon (CRBN) is the target protein receptor on the CRL4CRBN E3 ligase complex in the ubiquitin-proteasome system that includes Cul4, DDB1, and Roc1.1-3 CRBN is expressed in a variety of tissues, with the highest levels detected in T and B cells among other immune cells.4,5 Preclinical studies suggest that the immunomodulatory agents lenalidomide and pomalidomide co-opt CRBN to mediate the ubiquitination and proteasomal degradation of substrate proteins.2,3,6-11 In preclinical studies, this mechanism has been shown to underlie the anti-proliferative and immunomodulatory activities of these agents in malignancies including multiple myeloma, lymphoma, and del(5q) myelodysplastic syndromes.2,3,6-10 The redirection of CRBN by lenalidomide has been shown to have tumoricidal effects in non-Hodgkin lymphoma and multiple myeloma through inhibition of expression of oncogenes, such as IRF4.9,12,13 In del(5q) myelodysplastic syndromes, lenalidomide modulation of the CRL4CRBN complex has been shown to induce ubiquitination of casein kinase 1A1 (CK1α), resulting in its degredation.10 In multiple myeloma, pomalidomide exhibits tumorcidal, immunomodulatory, and anti-stromal support activities through modulation of the CRL4CRBN complex.14 Redirection of CRBN and the associated modulation of ubiquitination of proteins, as demonstrated in vitro, provide a molecular basis for the pharmacological activity of these immunomodulatory agents.

    CRBN, cereblon; Cul4, cullin 4; DDB1, DNA damage-binding protein 1; Roc1, regulator of cullins 1.

    View Related Molecules

    References

    1. Ito T, et al. Science. 2010;327:1345-1350. PMID: 20223979
    2. Lopez-Girona A, et al. Leukemia. 2012;26:2326-2335. PMID: 22552008
    3. Gandhi AK, et al. Br J Haematol. 2014;164:811-821. PMID: 24328678
    4. https://www.proteinatlas.org/ENSG00000113851-CRBN/tissue
    5. http://www.immgen.org/databrowser/index.html. Search term: CRBN.
    6. Xu Y, et al. Blood. 2009;114:338-345. PMID: 19417207
    7. Krönke J, et al. Science. 2014;343:301-305. PMID: 24292625
    8. Lu G, et al. Science. 2014;343:305-309. PMID: 24292623
    9. Zhang LH, et al. Br J Haematol. 2013;160:487-502. PMID: 23252516
    10. Fink EC, et al. Blood. 2014;124 [abstract 4].
    11. Hollenbach P, et al. Blood. 2014;124 [abstract 3606].
    12. Yang T, et al. Cancer Cell. 2012;21:727-737. PMID: 22698399
    13. Shaffer AL, et al. Clin Cancer Res. 2009;15:2954-2961. PMID: 19383829
    14. Quach H, et al. Leukemia. 2010;24:22-32. PMID: 19907437