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The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K)
The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders as they are key components in regulating cell signalling pathways. In an effort to make probe molecules available for further exploring these ta...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
RSC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583824/ https://www.ncbi.nlm.nih.gov/pubmed/37859710 http://dx.doi.org/10.1039/d3md00355h |
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author | Aldred, Gregory G. Rooney, Timothy P. C. Willems, Henriette M. G. Boffey, Helen K. Green, Christopher Winpenny, David Skidmore, John Clarke, Jonathan H. Andrews, Stephen P. |
author_facet | Aldred, Gregory G. Rooney, Timothy P. C. Willems, Henriette M. G. Boffey, Helen K. Green, Christopher Winpenny, David Skidmore, John Clarke, Jonathan H. Andrews, Stephen P. |
author_sort | Aldred, Gregory G. |
collection | PubMed |
description | The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders as they are key components in regulating cell signalling pathways. In an effort to make probe molecules available for further exploring these targets, we have previously reported PI5P4Kα-selective and PI5P4Kγ-selective ligands. Herein we report the rational design of PI5P4Kα/γ dual inhibitors, using knowledge gained during the development of selective inhibitors for these proteins. ARUK2007145 (39) is disclosed as a potent, cell-active probe molecule with ADMET properties amenable to conducting experiments in cells. |
format | Online Article Text |
id | pubmed-10583824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | RSC |
record_format | MEDLINE/PubMed |
spelling | pubmed-105838242023-10-19 The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) Aldred, Gregory G. Rooney, Timothy P. C. Willems, Henriette M. G. Boffey, Helen K. Green, Christopher Winpenny, David Skidmore, John Clarke, Jonathan H. Andrews, Stephen P. RSC Med Chem Chemistry The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders as they are key components in regulating cell signalling pathways. In an effort to make probe molecules available for further exploring these targets, we have previously reported PI5P4Kα-selective and PI5P4Kγ-selective ligands. Herein we report the rational design of PI5P4Kα/γ dual inhibitors, using knowledge gained during the development of selective inhibitors for these proteins. ARUK2007145 (39) is disclosed as a potent, cell-active probe molecule with ADMET properties amenable to conducting experiments in cells. RSC 2023-08-23 /pmc/articles/PMC10583824/ /pubmed/37859710 http://dx.doi.org/10.1039/d3md00355h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Aldred, Gregory G. Rooney, Timothy P. C. Willems, Henriette M. G. Boffey, Helen K. Green, Christopher Winpenny, David Skidmore, John Clarke, Jonathan H. Andrews, Stephen P. The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) |
title | The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) |
title_full | The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) |
title_fullStr | The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) |
title_full_unstemmed | The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) |
title_short | The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) |
title_sort | rational design of aruk2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (pi5p4k) |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583824/ https://www.ncbi.nlm.nih.gov/pubmed/37859710 http://dx.doi.org/10.1039/d3md00355h |
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