GSK2593074A (GSK'074) is a necroptosis inhibitor with dual targeting ability to both RIP1 and RIP3[1].
GSK2593074A (GSK'074; 0.01, 0.1, 1, 10, and 100 nM; 6 hours for MOVAS cells; 3 hours for L929 cells) completely rescues cells from necroptosis under different stimuli in both human and murine cells at IC50~3 nM. In multiple cell types including mouse SMCs, fibroblasts (L929), bone marrow derived macrophages (BMDM), and human colon epithelial cells (HT29), GSK2593074A inhibits necroptosis with an IC50 of ~3 nM[1].
Cell Viability Assay[1]
| Cell Line: | Mouse smooth muscle cell line MOVAS; Mouse fibroblast cell line L929 |
| Concentration: | 0.01, 0.1, 1, 10, and 100 nM |
| Incubation Time: | 6 hours for MOVAS cells; 3 hours for L929 cells |
| Result: | Inhibited MOVAS and L929 cells with the IC50 of 3 nM. |
GSK2593074A (GSK'074; 0.93 mg/kg/day; i.p. injection; 14 or 28 days) is administrated to Apoe-/- mice immediately following pump implantation. Compared to the DMSO group, GSK2593074A-treated mice show significantly alleviated aneurysm formation, reflected by a much smaller aortic dilatation (DMSO 85.39±15.76% vs GSK2593074A 36.28±5.76%; P<0.05) as well as a reduced abdominal aortic aneurysm (AAA) incidence (from 83.3 to 16.7%). GSK2593074A significantly decreases the extent of aortic expansion (DMSO 66.06±9.17% vs GSK2593074A 27.36±8.25%; P<0.05) [1].
| Animal Model: | Apoe-/- female mice (9-10 months)[1] |
| Dosage: | 0.93 mg/kg/day; 200 µL |
| Administration: | Daily i.p. injection; 14 or 28 days |
| Result: | Inhibited aneurysm formation in mouse models of aneurysms. |