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Substituted arylsulphonamides as inhibitors of perforin-mediated lysis
The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Editions Scientifiques Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500991/ https://www.ncbi.nlm.nih.gov/pubmed/28582670 http://dx.doi.org/10.1016/j.ejmech.2017.05.048 |
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author | Spicer, Julie A. Miller, Christian K. O'Connor, Patrick D. Jose, Jiney Huttunen, Kristiina M. Jaiswal, Jagdish K. Denny, William A. Akhlaghi, Hedieh Browne, Kylie A. Trapani, Joseph A. |
author_facet | Spicer, Julie A. Miller, Christian K. O'Connor, Patrick D. Jose, Jiney Huttunen, Kristiina M. Jaiswal, Jagdish K. Denny, William A. Akhlaghi, Hedieh Browne, Kylie A. Trapani, Joseph A. |
author_sort | Spicer, Julie A. |
collection | PubMed |
description | The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection. |
format | Online Article Text |
id | pubmed-5500991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Editions Scientifiques Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-55009912017-09-08 Substituted arylsulphonamides as inhibitors of perforin-mediated lysis Spicer, Julie A. Miller, Christian K. O'Connor, Patrick D. Jose, Jiney Huttunen, Kristiina M. Jaiswal, Jagdish K. Denny, William A. Akhlaghi, Hedieh Browne, Kylie A. Trapani, Joseph A. Eur J Med Chem Research Paper The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection. Editions Scientifiques Elsevier 2017-09-08 /pmc/articles/PMC5500991/ /pubmed/28582670 http://dx.doi.org/10.1016/j.ejmech.2017.05.048 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Spicer, Julie A. Miller, Christian K. O'Connor, Patrick D. Jose, Jiney Huttunen, Kristiina M. Jaiswal, Jagdish K. Denny, William A. Akhlaghi, Hedieh Browne, Kylie A. Trapani, Joseph A. Substituted arylsulphonamides as inhibitors of perforin-mediated lysis |
title | Substituted arylsulphonamides as inhibitors of perforin-mediated lysis |
title_full | Substituted arylsulphonamides as inhibitors of perforin-mediated lysis |
title_fullStr | Substituted arylsulphonamides as inhibitors of perforin-mediated lysis |
title_full_unstemmed | Substituted arylsulphonamides as inhibitors of perforin-mediated lysis |
title_short | Substituted arylsulphonamides as inhibitors of perforin-mediated lysis |
title_sort | substituted arylsulphonamides as inhibitors of perforin-mediated lysis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500991/ https://www.ncbi.nlm.nih.gov/pubmed/28582670 http://dx.doi.org/10.1016/j.ejmech.2017.05.048 |
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