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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Optimization of Imidazo[4,5‑b]pyridine-Based Kinase Inhibitors: Identification of a Dual FLT3/Aurora Kinase Inhibitor as an Orally Bioavailable Preclinical Development Candidate for the Treatment of Acute Myeloid Leukemia
|
|---|---|
| Published in |
Journal of Medicinal Chemistry, October 2012
|
| DOI | 10.1021/jm300952s |
| Pubmed ID | |
| Authors |
Vassilios Bavetsias, Simon Crumpler, Chongbo Sun, Sian Avery, Butrus Atrash, Amir Faisal, Andrew S. Moore, Magda Kosmopoulou, Nathan Brown, Peter W. Sheldrake, Katherine Bush, Alan Henley, Gary Box, Melanie Valenti, Alexis de Haven Brandon, Florence I. Raynaud, Paul Workman, Suzanne A. Eccles, Richard Bayliss, Spiros Linardopoulos, Julian Blagg |
| Abstract |
Optimization of the imidazo[4,5-b]pyridine-based series of Aurora kinase inhibitors led to the identification of 6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (27e), a potent inhibitor of Aurora kinases (Aurora-A K(d) = 7.5 nM, Aurora-B K(d) = 48 nM), FLT3 kinase (K(d) = 6.2 nM), and FLT3 mutants including FLT3-ITD (K(d) = 38 nM) and FLT3(D835Y) (K(d) = 14 nM). FLT3-ITD causes constitutive FLT3 kinase activation and is detected in 20-35% of adults and 15% of children with acute myeloid leukemia (AML), conferring a poor prognosis in both age groups. In an in vivo setting, 27e strongly inhibited the growth of a FLT3-ITD-positive AML human tumor xenograft (MV4-11) following oral administration, with in vivo biomarker modulation and plasma free drug exposures consistent with dual FLT3 and Aurora kinase inhibition. Compound 27e, an orally bioavailable dual FLT3 and Aurora kinase inhibitor, was selected as a preclinical development candidate for the treatment of human malignancies, in particular AML, in adults and children. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Denmark | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 89 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 2% |
| Japan | 1 | 1% |
| Unknown | 86 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 27 | 30% |
| Student > Ph. D. Student | 18 | 20% |
| Student > Master | 8 | 9% |
| Student > Bachelor | 7 | 8% |
| Other | 6 | 7% |
| Other | 8 | 9% |
| Unknown | 15 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 29 | 33% |
| Biochemistry, Genetics and Molecular Biology | 13 | 15% |
| Agricultural and Biological Sciences | 11 | 12% |
| Medicine and Dentistry | 8 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 6% |
| Other | 6 | 7% |
| Unknown | 17 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. 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 30 May 2023.
All research outputs
#3,013,987
of 23,248,929 outputs
Outputs from Journal of Medicinal Chemistry
#2,894
of 22,218 outputs
Outputs of similar age
#21,493
of 174,155 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#23
of 170 outputs
Altmetric has tracked 23,248,929 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 22,218 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one has done well, scoring higher than 86% 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 174,155 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 170 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.