| Title |
Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo
|
|---|---|
| Published in |
Leukemia, January 2017
|
| DOI | 10.1038/leu.2017.46 |
| Pubmed ID | |
| Authors |
A Chaturvedi, L Herbst, S Pusch, L Klett, R Goparaju, D Stichel, S Kaulfuss, O Panknin, K Zimmermann, L Toschi, R Neuhaus, A Haegebarth, H Rehwinkel, H Hess-Stumpp, M Bauser, T Bochtler, E A Struys, A Sharma, A Bakkali, R Geffers, M M Araujo-Cruz, F Thol, R Gabdoulline, A Ganser, A D Ho, A von Deimling, K Rippe, M Heuser, A Krämer |
| Abstract |
Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are frequently found in several human cancer types including acute myeloid leukemia (AML) and lead to the production of high levels of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). Here we report the characterization of BAY1436032, a novel pan-mutant IDH1 inhibitor, both in vitro and in vivo. BAY1436032 specifically inhibits R-2HG production and colony growth, and induces myeloid differentiation of AML cells carrying IDH1R132H, IDH1R132C, IDH1R132G, IDH1R132L and IDH1R132S mutations. In addition, the compound impacts on DNA methylation and attenuates histone hypermethylation. Oral administration of BAY1436032 led to leukemic blast clearance, myeloid differentiation, depletion of leukemic stem cells and prolonged survival in two independent patient-derived xenograft IDH1 mutant AML mouse models. Together, BAY1436032 is highly effective against all major types of IDH1 mutant AML.Leukemia advance online publication, 24 February 2017; doi:10.1038/leu.2017.46. |
X Demographics
The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 11% |
| Saudi Arabia | 1 | 11% |
| United Kingdom | 1 | 11% |
| Unknown | 6 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 44% |
| Scientists | 3 | 33% |
| Science communicators (journalists, bloggers, editors) | 2 | 22% |
Mendeley readers
The data shown below were compiled from readership statistics for 87 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 87 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 24 | 28% |
| Student > Master | 11 | 13% |
| Student > Ph. D. Student | 11 | 13% |
| Student > Bachelor | 7 | 8% |
| Other | 5 | 6% |
| Other | 9 | 10% |
| Unknown | 20 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 22 | 25% |
| Medicine and Dentistry | 16 | 18% |
| Agricultural and Biological Sciences | 10 | 11% |
| Chemistry | 7 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 5% |
| Other | 8 | 9% |
| Unknown | 20 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 53. 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 15 August 2023.
All research outputs
#750,873
of 24,257,370 outputs
Outputs from Leukemia
#124
of 5,256 outputs
Outputs of similar age
#17,193
of 427,490 outputs
Outputs of similar age from Leukemia
#5
of 85 outputs
Altmetric has tracked 24,257,370 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,256 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.3. This one has done particularly well, scoring higher than 97% of its peers.
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We're also able to compare this research output to 85 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 95% of its contemporaries.