TY  - JOUR
AU  - Spicer, JA
AU  - Miller, CK
AU  - O'Connor, PD
AU  - Jose, J
AU  - Huttunen, KM
AU  - Jaiswal, JK
AU  - Denny, WA
AU  - Akhlaghi, H
AU  - Browne, KA
AU  - Trapani, JA
Y2  - 2021/02/04
Y1  - 2017/09/08
SN  - 0223-5234
UR  - http://hdl.handle.net/11343/259553
AB  - 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.
LA  - English
PB  - ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
T1  - Substituted arylsulphonamides as inhibitors of perforin-mediated lysis
DO  - 10.1016/j.ejmech.2017.05.048
IS  - European Journal of Medicinal Chemistry
VL  - 137
SP  - 139-155
L1  - /bitstream/handle/11343/259553/PMC5500991.pdf?sequence=1&isAllowed=y
ER  -