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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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2023
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.
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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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