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FIKK Kinase, a Ser/Thr Kinase Important to Malaria Parasites, Is Inhibited by Tyrosine Kinase Inhibitors
[Image: see text] A relatively high-affinity inhibitor of FIKK kinase from the malaria parasite Plasmodium vivax was identified by in vitro assay of recombinant kinase. The FIKK kinase family is unique to parasitic organisms of the Apicomplexan order and has been shown to be critical in malaria para...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044879/ https://www.ncbi.nlm.nih.gov/pubmed/30023525 http://dx.doi.org/10.1021/acsomega.7b00997 |
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author | Lin, Benjamin C. Harris, Darcy R. Kirkman, Lucy M. D. Perez, Astrid M. Qian, Yiwen Schermerhorn, Janse T. Hong, Min Y. Winston, Dennis S. Xu, Lingyin Brandt, Gabriel S. |
author_facet | Lin, Benjamin C. Harris, Darcy R. Kirkman, Lucy M. D. Perez, Astrid M. Qian, Yiwen Schermerhorn, Janse T. Hong, Min Y. Winston, Dennis S. Xu, Lingyin Brandt, Gabriel S. |
author_sort | Lin, Benjamin C. |
collection | PubMed |
description | [Image: see text] A relatively high-affinity inhibitor of FIKK kinase from the malaria parasite Plasmodium vivax was identified by in vitro assay of recombinant kinase. The FIKK kinase family is unique to parasitic organisms of the Apicomplexan order and has been shown to be critical in malaria parasites. The recombinant kinase domain was expressed and screened against a small molecule library, revealing a number of tyrosine kinase inhibitors that block FIKK kinase activity. A family of tyrphostins was further investigated, to begin exploring the FIKK kinase pharmacophore. Finally, emodin was identified as a relatively high-affinity FIKK kinase inhibitor, identifying this family of anthraquinones as potential lead compounds for the development of antimalarials targeting the FIKK kinase. |
format | Online Article Text |
id | pubmed-6044879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-60448792018-07-16 FIKK Kinase, a Ser/Thr Kinase Important to Malaria Parasites, Is Inhibited by Tyrosine Kinase Inhibitors Lin, Benjamin C. Harris, Darcy R. Kirkman, Lucy M. D. Perez, Astrid M. Qian, Yiwen Schermerhorn, Janse T. Hong, Min Y. Winston, Dennis S. Xu, Lingyin Brandt, Gabriel S. ACS Omega [Image: see text] A relatively high-affinity inhibitor of FIKK kinase from the malaria parasite Plasmodium vivax was identified by in vitro assay of recombinant kinase. The FIKK kinase family is unique to parasitic organisms of the Apicomplexan order and has been shown to be critical in malaria parasites. The recombinant kinase domain was expressed and screened against a small molecule library, revealing a number of tyrosine kinase inhibitors that block FIKK kinase activity. A family of tyrphostins was further investigated, to begin exploring the FIKK kinase pharmacophore. Finally, emodin was identified as a relatively high-affinity FIKK kinase inhibitor, identifying this family of anthraquinones as potential lead compounds for the development of antimalarials targeting the FIKK kinase. American Chemical Society 2017-10-11 /pmc/articles/PMC6044879/ /pubmed/30023525 http://dx.doi.org/10.1021/acsomega.7b00997 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Lin, Benjamin C. Harris, Darcy R. Kirkman, Lucy M. D. Perez, Astrid M. Qian, Yiwen Schermerhorn, Janse T. Hong, Min Y. Winston, Dennis S. Xu, Lingyin Brandt, Gabriel S. FIKK Kinase, a Ser/Thr Kinase Important to Malaria Parasites, Is Inhibited by Tyrosine Kinase Inhibitors |
title | FIKK Kinase, a Ser/Thr Kinase Important to Malaria
Parasites, Is Inhibited by Tyrosine Kinase Inhibitors |
title_full | FIKK Kinase, a Ser/Thr Kinase Important to Malaria
Parasites, Is Inhibited by Tyrosine Kinase Inhibitors |
title_fullStr | FIKK Kinase, a Ser/Thr Kinase Important to Malaria
Parasites, Is Inhibited by Tyrosine Kinase Inhibitors |
title_full_unstemmed | FIKK Kinase, a Ser/Thr Kinase Important to Malaria
Parasites, Is Inhibited by Tyrosine Kinase Inhibitors |
title_short | FIKK Kinase, a Ser/Thr Kinase Important to Malaria
Parasites, Is Inhibited by Tyrosine Kinase Inhibitors |
title_sort | fikk kinase, a ser/thr kinase important to malaria
parasites, is inhibited by tyrosine kinase inhibitors |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044879/ https://www.ncbi.nlm.nih.gov/pubmed/30023525 http://dx.doi.org/10.1021/acsomega.7b00997 |
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