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Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs

Overview of attention for article published in Nature Structural & Molecular Biology, August 2014
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
4 news outlets
blogs
1 blog
twitter
14 tweeters
patent
33 patents

Citations

dimensions_citation
266 Dimensions

Readers on

mendeley
324 Mendeley
Title
Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs
Published in
Nature Structural & Molecular Biology, August 2014
DOI 10.1038/nsmb.2874
Pubmed ID
Authors

Philip P Chamberlain, Antonia Lopez-Girona, Karen Miller, Gilles Carmel, Barbra Pagarigan, Barbara Chie-Leon, Emily Rychak, Laura G Corral, Yan J Ren, Maria Wang, Mariko Riley, Silvia L Delker, Takumi Ito, Hideki Ando, Tomoyuki Mori, Yoshinori Hirano, Hiroshi Handa, Toshio Hakoshima, Thomas O Daniel, Brian E Cathers

Abstract

The Cul4-Rbx1-DDB1-Cereblon E3 ubiquitin ligase complex is the target of thalidomide, lenalidomide and pomalidomide, therapeutically important drugs for multiple myeloma and other B-cell malignancies. These drugs directly bind Cereblon (CRBN) and promote the recruitment of substrates Ikaros (IKZF1) and Aiolos (IKZF3) to the E3 complex, thus leading to substrate ubiquitination and degradation. Here we present the crystal structure of human CRBN bound to DDB1 and the drug lenalidomide. A hydrophobic pocket in the thalidomide-binding domain (TBD) of CRBN accommodates the glutarimide moiety of lenalidomide, whereas the isoindolinone ring is exposed to solvent. We also solved the structures of the mouse TBD in the apo state and with thalidomide or pomalidomide. Site-directed mutagenesis in lentiviral-expression myeloma models showed that key drug-binding residues are critical for antiproliferative effects.

Twitter Demographics

The data shown below were collected from the profiles of 14 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 324 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 4 1%
Germany 2 <1%
Japan 2 <1%
Belgium 1 <1%
France 1 <1%
India 1 <1%
Denmark 1 <1%
Brazil 1 <1%
United Kingdom 1 <1%
Other 0 0%
Unknown 310 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 77 24%
Student > Ph. D. Student 62 19%
Student > Master 34 10%
Student > Bachelor 31 10%
Other 23 7%
Other 53 16%
Unknown 44 14%
Readers by discipline Count As %
Chemistry 82 25%
Biochemistry, Genetics and Molecular Biology 71 22%
Agricultural and Biological Sciences 57 18%
Medicine and Dentistry 25 8%
Pharmacology, Toxicology and Pharmaceutical Science 19 6%
Other 16 5%
Unknown 54 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 60. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 August 2021.
All research outputs
#470,779
of 18,838,632 outputs
Outputs from Nature Structural & Molecular Biology
#168
of 2,963 outputs
Outputs of similar age
#5,646
of 204,387 outputs
Outputs of similar age from Nature Structural & Molecular Biology
#1
of 36 outputs
Altmetric has tracked 18,838,632 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,963 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.5. This one has done particularly well, scoring higher than 94% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 204,387 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.