RIP1/RIP3/MLKL activator 1 (Compound 6i) is a potent anti-glioma agent. RIP1/RIP3/MLKL activator 1 induces Necroptosis through RIP1/RIP3/MLKL pathway. RIP1/RIP3/MLKL activator 1 exerts acceptable BBB permeability[1].
RIP1/RIP3/MLKL activator 1 (Compound 6i) (96 h) shows antiproliferative activities in human glioma cell lines[1].
RIP1/RIP3/MLKL activator 1 (0-4 µM, 0-72 h) exhibits remarkable antiproliferative activity for U251 cells in a time- and concentration-dependent manner[1].
RIP1/RIP3/MLKL activator 1 (10 µM, 0-72 h) shows acceptable stability[1].
RIP1/RIP3/MLKL activator 1 (0-2 µM, 24 h) effectively inhibits the migration of U251 cells[1].
RIP1/RIP3/MLKL activator 1 induces necroptosis through RIP1/RIP3/MLKL pathway, and induces mitochondrial depolarization in U251 cells[1].
RIP1/RIP3/MLKL activator 1 could not induce apoptosis in U251 cells[1].
Cell Proliferation Assay[1]
| Cell Line: | A172, LN229, U87, U251 and L02 cell lines |
| Concentration: | 0-4 µM for U251 cells |
| Incubation Time: | 96 h; 24, 48, and 72 h for U251 cells |
| Result: | Showed antiproliferative activity with IC50 values of 3.03 ± 0.70, 1.78 ± 0.79, 1.22 ± 0.89, 0.94 ± 0.45, and 0.99 ± 0.46 µM against A172, LN229, U87, U251 and L02 cells, respectively. Time- and concentration-dependently inhibited the growth in U251 cells. |
Western Blot Analysis[1]
| Cell Line: | U251 |
| Concentration: | 0, 0.5, 1, 2, and 4 µM |
| Incubation Time: | 24 or 48 h |
| Result: | Concentration-dependently upregulated the expression of p-RIP1, RIP1, p-RIP3, RIP3, p-MLKL, and MLKL at 24 or 48 h. |
RIP1/RIP3/MLKL activator 1 (Compound 6i) (2.50 ng/tail; i.v.; 48 h) inhibits U251 cell proliferation in vivo and exerts acceptable BBB permeability[1].
| Animal Model: | Zebrafish wide-type AB strain; 200 CM-DiI labeled U251 cells were transplanted into yolk sac of each wild-type zebrafish embryos at 2 dpf (2 days postfertilization)[1] |
| Dosage: | 2.50 ng/tail |
| Administration: | Microinjection; 48 h |
| Result: | Remarkably reduced the U251 xenografts fluorescence intensity. |
[1]. Yao Feng, et al. Synthesis and biological evaluation of celastrol derivatives as potential anti-glioma agents by activating RIP1/RIP3/MLKL pathway to induce necroptosis. Eur J Med Chem. 2022 Feb 5;229:114070.