Substituted arylsulphonamides as inhibitors of perforin-mediated lysis
| Autor: | Joseph A. Trapani, Christian K. Miller, Jagdish K. Jaiswal, Kristiina M. Huttunen, Patrick D. O'Connor, Jiney Jose, William A. Denny, Hedieh Akhlaghi, Julie Ann Spicer, Kylie A. Browne |
|---|---|
| Přispěvatelé: | School of Pharmacy, Activities |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Bioisostere chemical and pharmacologic phenomena Jurkat cells Jurkat Cells Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Immune system Arylsulphonamide Drug Discovery medicine Humans Cytotoxicity Immunosuppressant Pharmacology Sulfonamides Dose-Response Relationship Drug Molecular Structure biology Perforin Chemistry Organic Chemistry General Medicine Perforin inhibitor medicine.disease 3. Good health Transplant rejection Killer Cells Natural Granzyme B 030104 developmental biology Graft-versus-host disease Lytic cycle 030220 oncology & carcinogenesis Immunology biology.protein Cancer research Research Paper |
| Zdroj: | European Journal of Medicinal Chemistry |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2017.05.048 |
| Popis: | 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. final draft peerReviewed |
| Databáze: | OpenAIRE |
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