| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Cell lines | HT-29 cells |
Preparation Method | Relative viability of human HT-29 cells 24 hr posttreatment (hpt) with TNF (10 ng/ml), zVAD-fmk (zVAD; 20 μM), and SMAC007 (100 nM) in the presence of increasing concentrations of GSK-872, assessed by determining ATP levels (mean ± range is shown) compared to cells treated with vehicle (DMSO) alone. |
Reaction Conditions | 0.01, 0.03 , 0.1, 0.3, 1, and 3 μM；24 hours |
Applications | When evaluated in cell culture using human HT-29 cells,GSK-872 ( 0.01-3 μM; 24 hours) blocks TNF-induced necroptosis in human HT-29 cells in a concentration-dependent manne[1]. |
Animal models | Sprague-Dawley male rats with 300–320 g body weight |
Preparation Method | GSK-872 was diluted with 1% DMSO to a concentration of 25 mM, and 6 μL of GSK-872 or diluted DMSO was administrated by a syringe pump at 30 min after SAH as previously described, Neurological function (n = 24) was evaluated at 24 h and 72 h after operation. Brain edema (n = 6), western blot (n = 6), PI staining (n = 6) and HMGB1 immunofluorescence (n = 6) were evaluated at 72 h after SAH. |
Dosage form | 6ul 25mM; 24 h and 72 h |
Applications | GSK-872 hydrochloride (25 mM; intracerebroventricular injection) can attenuate brain edema and improve neurological function following subarachnoid hemorrhage (SAH) and reduce the number of necrotic cells. GSK-872 hydrochloride can also decrease the protein levels of RIPK3 and MLKL, and cytoplasmic translocation and expression of HMGB1, an important pro-inflammatory protein[2]. |
| 文献引用 | |
| 产品描述 | GSK-872 is a RIPK3 inhibitor. GSK-872 decreases the RIPK3-mediated necroptosis and subsequent cytoplasmic translocation and expression of HMGB1, as well as ameliorates brain edema and neurological deficits in early brain injury[5]. GSK-872 bound RIP3 kinase domain with high affinity (IC50= 1.8 nM) and inhibited kinase activity (IC50= 1.3 nM)[1]. GSK-872 prevented virus-induced necrosis, a pathway dependent on DAI-RIP3 complex formation,GSK-872 blocked TLR3-induced necrosis induced in fibroblasts by poly(I:C) in the presence of Z-VAD-fmk, Both virus- and TLR3-induced necrosis proceed independently of RIP1 kinase inhibition by Nec-1 but sensitive to inhibition by GSK-872[2,3,4]. Pharmacological inhibitor GSK-872 enhanced insulin signaling in vitro and in vivo, which contributing to improve insulin sensitivity[9]. When evaluated in cell culture using human HT-29 cells, GSK-872 bind the kinase domain and inhibit kinase activity with high specificity, targeting a broader range of pronecrotic stimuli[1]. RIP3i compounds GSK-872 blocked TNF-induced necroptosis in a concentration-dependent manner . In cell-based assays, there was a 100- to 1,000-fold shift in the IC50compared to the cell-free biochemical assays. GSK-872 blocked necroptosis in primary human neutrophils isolated from whole blood，and blocked necroptosis in mouse cells. Mouse bone-marrow-derived macrophages (BMDMs) or thioglycolate-elicited peritoneal macrophages (PECs), as well as 3T3SA fibroblasts, were also protected by GSK-872 concentrations . GSK-872 significantly reduced brain edema and improved neurological function in SAH rats, and reduced the number of necrotic cells. The exact mechanism of GSK-872 induced neuroprotective effect against SAH was identified[6,7].Inhibiting of RIPK3 by GSK-872 could attenuate RIPK3-dependent necroptosis, decrease brain edema, and improve neurological function after SAH. GSK-872 also improves hepatic steatosis and liver injury in mice fed with HFCD after CIH exposure[8]. References: |
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