Unknown

Dataset Information

0

Benzenesulphonamide inhibitors of the cytolytic protein perforin.


ABSTRACT: 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.

SUBMITTER: Spicer JA 

PROVIDER: S-EPMC5303009 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3865801 | biostudies-literature
| S-EPMC4706532 | biostudies-literature
| S-EPMC5500991 | biostudies-literature
| S-EPMC7034112 | biostudies-literature
| S-EPMC6759663 | biostudies-literature
| S-EPMC5561019 | biostudies-other
| S-EPMC286441 | biostudies-other
| S-EPMC2667449 | biostudies-literature
| S-EPMC7423880 | biostudies-literature
| S-EPMC4318580 | biostudies-literature