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  - 2020/12/21
Y1  - 2017/02/15
SN  - 0960-894X
UR  - http://hdl.handle.net/11343/257547
AB  - The pore-forming protein perforin is a key component of mammalian cell-mediated immunity and essential to the pathway that allows elimination of virus-infected and transformed cells. Perforin activity has also been implicated in certain auto-immune conditions and therapy-induced conditions such as allograft rejection and graft versus host disease. An inhibitor of perforin activity could be used as a highly specific immunosuppressive treatment for these conditions, with reduced side-effects compared to currently accepted therapies. Previously identified first-in-class inhibitors based on a 2-thioxoimidazolidin-4-one core show suboptimal physicochemical properties and toxicity toward the natural killer (NK) cells that secrete perforin in vivo. The current benzenesulphonamide-based series delivers a non-toxic bioisosteric replacement possessing improved solubility.
LA  - English
PB  - PERGAMON-ELSEVIER SCIENCE LTD
T1  - Benzenesulphonamide inhibitors of the cytolytic protein perforin
DO  - 10.1016/j.bmcl.2016.12.057
IS  - Bioorganic and Medicinal Chemistry Letters
VL  - 27
IS  - 4
SP  - 1050-1054
L1  - /bitstream/handle/11343/257547/PMC5303009.pdf?sequence=1&isAllowed=y
ER  -