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The Design and Synthesis of Potent and Selective Inhibitors of Trypanosoma brucei Glycogen Synthase Kinase 3 for the Treatment of Human African Trypanosomiasis
[Image: see text] Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness. We report the synthesis and biological evaluation of aminopyrazole derivatives as Trypanosoma brucei GSK3 short inhibitors. Low n...
| Autores principales: | , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical
Society
2014
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175002/ https://www.ncbi.nlm.nih.gov/pubmed/25198388 http://dx.doi.org/10.1021/jm500239b |
| _version_ | 1782336435410436096 |
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| author | Urich, Robert Grimaldi, Raffaella Luksch, Torsten Frearson, Julie A. Brenk, Ruth Wyatt, Paul G. |
| author_facet | Urich, Robert Grimaldi, Raffaella Luksch, Torsten Frearson, Julie A. Brenk, Ruth Wyatt, Paul G. |
| author_sort | Urich, Robert |
| collection | PubMed |
| description | [Image: see text] Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness. We report the synthesis and biological evaluation of aminopyrazole derivatives as Trypanosoma brucei GSK3 short inhibitors. Low nanomolar inhibitors, which had high selectivity over the off-target human CDK2 and good selectivity over human GSK3β enzyme, have been prepared. These potent kinase inhibitors demonstrated low micromolar levels of inhibition of the Trypanosoma brucei brucei parasite grown in culture. |
| format | Online Article Text |
| id | pubmed-4175002 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2014 |
| publisher | American Chemical
Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-41750022014-09-27 The Design and Synthesis of Potent and Selective Inhibitors of Trypanosoma brucei Glycogen Synthase Kinase 3 for the Treatment of Human African Trypanosomiasis Urich, Robert Grimaldi, Raffaella Luksch, Torsten Frearson, Julie A. Brenk, Ruth Wyatt, Paul G. J Med Chem [Image: see text] Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness. We report the synthesis and biological evaluation of aminopyrazole derivatives as Trypanosoma brucei GSK3 short inhibitors. Low nanomolar inhibitors, which had high selectivity over the off-target human CDK2 and good selectivity over human GSK3β enzyme, have been prepared. These potent kinase inhibitors demonstrated low micromolar levels of inhibition of the Trypanosoma brucei brucei parasite grown in culture. American Chemical Society 2014-09-08 2014-09-25 /pmc/articles/PMC4175002/ /pubmed/25198388 http://dx.doi.org/10.1021/jm500239b Text en Copyright © 2014 American Chemical Society Terms of Use CC-BY (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) |
| spellingShingle | Urich, Robert Grimaldi, Raffaella Luksch, Torsten Frearson, Julie A. Brenk, Ruth Wyatt, Paul G. The Design and Synthesis of Potent and Selective Inhibitors of Trypanosoma brucei Glycogen Synthase Kinase 3 for the Treatment of Human African Trypanosomiasis |
| title | The Design and Synthesis of
Potent and Selective Inhibitors
of Trypanosoma brucei Glycogen Synthase
Kinase 3 for the Treatment of Human African Trypanosomiasis |
| title_full | The Design and Synthesis of
Potent and Selective Inhibitors
of Trypanosoma brucei Glycogen Synthase
Kinase 3 for the Treatment of Human African Trypanosomiasis |
| title_fullStr | The Design and Synthesis of
Potent and Selective Inhibitors
of Trypanosoma brucei Glycogen Synthase
Kinase 3 for the Treatment of Human African Trypanosomiasis |
| title_full_unstemmed | The Design and Synthesis of
Potent and Selective Inhibitors
of Trypanosoma brucei Glycogen Synthase
Kinase 3 for the Treatment of Human African Trypanosomiasis |
| title_short | The Design and Synthesis of
Potent and Selective Inhibitors
of Trypanosoma brucei Glycogen Synthase
Kinase 3 for the Treatment of Human African Trypanosomiasis |
| title_sort | design and synthesis of
potent and selective inhibitors
of trypanosoma brucei glycogen synthase
kinase 3 for the treatment of human african trypanosomiasis |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175002/ https://www.ncbi.nlm.nih.gov/pubmed/25198388 http://dx.doi.org/10.1021/jm500239b |
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