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Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097

Overview of attention for article published in Molecular Cancer Therapeutics, July 2015
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (65th percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

Mentioned by

patent
2 patents

Citations

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24 Dimensions

Readers on

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27 Mendeley
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Title
Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097
Published in
Molecular Cancer Therapeutics, July 2015
DOI 10.1158/1535-7163.mct-15-0429
Pubmed ID
Authors

E. Weisberg, E. Halilovic, V. G. Cooke, A. Nonami, T. Ren, T. Sanda, I. Simkin, J. Yuan, B. Antonakos, L. Barys, M. Ito, R. Stone, I. Galinsky, K. Cowens, E. Nelson, M. Sattler, S. Jeay, J. U. Wuerthner, S. M. McDonough, M. Wiesmann, J. D. Griffin

Abstract

The tumor suppressor, p53, is a key regulator of apoptosis and functions upstream in the apoptotic cascade by both indirectly and directly regulating Bcl-2 family proteins. In cells expressing wild-type (wt) p53, the HDM2 protein binds to p53 and blocks its activity. Inhibition of HDM2:p53 interaction activates p53 and causes apoptosis or cell cycle arrest. Here, we investigated the ability of the novel HDM2 inhibitor, CGM097, to potently and selectively kill wt p53-expressing AML cells. The anti-leukemic effects of CGM097 were studied using cell-based proliferation assays (human AML cell lines, primary AML patient cells and normal bone marrow samples), apoptosis and cell cycle assays, ELISA, immunoblotting, and an AML patient-derived in vivo mouse model. CGM097 potently and selectively inhibited the proliferation of human AML cell lines and the majority of primary AML cells expressing wt p53, but not mutant p53, in a target-specific manner. Several patient samples that harbored mutant p53 were comparatively unresponsive to CGM097. Synergy was observed when CGM097 was combined with FLT3 inhibition against oncogenic FLT3-expressing cells cultured both in the absence as well as the presence of cytoprotective stromal-secreted cytokines, as well as when combined with MEK inhibition in cells with activated MAPK signaling. Finally, CGM097 was effective in reducing leukemia burden in vivo. These data suggest that CGM097 is a promising treatment for AML characterized as harboring wt p53 as a single agent, as well as in combination with other therapies targeting oncogene-activated pathways that drive AML.

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 26%
Student > Bachelor 4 15%
Student > Postgraduate 3 11%
Professor > Associate Professor 3 11%
Student > Master 3 11%
Other 4 15%
Unknown 3 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 22%
Biochemistry, Genetics and Molecular Biology 5 19%
Medicine and Dentistry 5 19%
Pharmacology, Toxicology and Pharmaceutical Science 3 11%
Chemistry 3 11%
Other 2 7%
Unknown 3 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 24 May 2018.
All research outputs
#3,821,405
of 12,978,017 outputs
Outputs from Molecular Cancer Therapeutics
#894
of 2,570 outputs
Outputs of similar age
#85,948
of 267,809 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#7
of 39 outputs
Altmetric has tracked 12,978,017 research outputs across all sources so far. This one is in the 49th percentile – i.e., 49% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,570 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 39th percentile – i.e., 39% of its peers scored the same or lower than it.
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 267,809 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.