| Title |
Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo
|
|---|---|
| Published in |
Acta Neuropathologica, January 2017
|
| DOI | 10.1007/s00401-017-1677-y |
| Pubmed ID | |
| Authors |
Stefan Pusch, Sonja Krausert, Viktoria Fischer, Jörg Balss, Martina Ott, Daniel Schrimpf, David Capper, Felix Sahm, Jessica Eisel, Ann-Christin Beck, Manfred Jugold, Viktoria Eichwald, Stefan Kaulfuss, Olaf Panknin, Hartmut Rehwinkel, Katja Zimmermann, Roman C. Hillig, Judith Guenther, Luisella Toschi, Roland Neuhaus, Andrea Haegebart, Holger Hess-Stumpp, Markus Bauser, Wolfgang Wick, Andreas Unterberg, Christel Herold-Mende, Michael Platten, Andreas von Deimling |
| Abstract |
Mutations in codon 132 of isocitrate dehydrogenase (IDH) 1 are frequent in diffuse glioma, acute myeloid leukemia, chondrosarcoma and intrahepatic cholangiocarcinoma. These mutations result in a neomorphic enzyme specificity which leads to a dramatic increase of intracellular D-2-hydroxyglutarate (2-HG) in tumor cells. Therefore, mutant IDH1 protein is a highly attractive target for inhibitory drugs. Here, we describe the development and properties of BAY 1436032, a pan-inhibitor of IDH1 protein with different codon 132 mutations. BAY 1436032 strongly reduces 2-HG levels in cells carrying IDH1-R132H, -R132C, -R132G, -R132S and -R132L mutations. Cells not carrying IDH mutations were unaffected. BAY 1436032 did not exhibit toxicity in vitro or in vivo. The pharmacokinetic properties of BAY 1436032 allow for oral administration. In two independent experiments, BAY 1436032 has been shown to significantly prolong survival of mice intracerebrally transplanted with human astrocytoma carrying the IDH1R132H mutation. In conclusion, we developed a pan-inhibitor targeting tumors with different IDH1R132 mutations. |
Mendeley readers
The data shown below were compiled from readership statistics for 118 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 118 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 25 | 21% |
| Student > Ph. D. Student | 22 | 19% |
| Student > Master | 15 | 13% |
| Student > Bachelor | 9 | 8% |
| Student > Postgraduate | 6 | 5% |
| Other | 13 | 11% |
| Unknown | 28 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 24 | 20% |
| Medicine and Dentistry | 22 | 19% |
| Chemistry | 13 | 11% |
| Agricultural and Biological Sciences | 8 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 7% |
| Other | 12 | 10% |
| Unknown | 31 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 83. 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
#476,840
of 24,257,963 outputs
Outputs from Acta Neuropathologica
#55
of 2,466 outputs
Outputs of similar age
#10,940
of 426,379 outputs
Outputs of similar age from Acta Neuropathologica
#5
of 34 outputs
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We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.