GSK-872 |
| Catalog No.GC19175 |
GSK-872 is a RIPK3 inhibitor.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1346546-69-7
Sample solution is provided at 25 µL, 10mM.
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 IC50 compared 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:
[1]: Mandal P, Berger SB, et, al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol Cell. 2014 Nov 20;56(4):481-95. doi: 10.1016/j.molcel.2014.10.021. Epub 2014 Nov 20. PMID: 25459880; PMCID: PMC4512186.
[2]:Kaiser WJ, Sridharan H, et, al. Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J Biol Chem. 2013 Oct 25;288(43):31268-79. doi: 10.1074/jbc.M113.462341. Epub 2013 Sep 9. PMID: 24019532; PMCID: PMC3829437.
[3]: Arora D, Siddiqui MH, et, al. Deltamethrin induced RIPK3-mediated caspase-independent non-apoptotic cell death in rat primary hepatocytes. Biochem Biophys Res Commun. 2016 Oct 14;479(2):217-223. doi:
[4]: He S, Liang Y, Shao F, Wang X. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20054-9. doi: 10.1073/pnas.1116302108. Epub 2011 Nov 28. PMID: 22123964; PMCID: PMC3250173.
[5]: Chen T, Pan H, et, al. Inhibiting of RIPK3 attenuates early brain injury following subarachnoid hemorrhage: Possibly through alleviating necroptosis. Biomed Pharmacother. 2018 Nov;107:563-570. doi: 10.1016/j.biopha.2018.08.056. Epub 2018 Aug 14. PMID: 30114640.
[6]: Chen S, Lv X, et, al.RIPK1/RIPK3/MLKL-mediated necroptosis contributes to compression-induced rat nucleus pulposus cells death. Apoptosis. 2017 May;22(5):626-638. doi: 10.1007/s10495-017-1358-2. PMID: 28289909.
[7]: Liu T, Zhao DX, et, al. Therapeutic hypothermia attenuates tissue damage and cytokine expression after traumatic brain injury by inhibiting necroptosis in the rat. Sci Rep. 2016 Apr 15;6:24547. doi: 10.1038/srep24547. PMID: 27080932; PMCID: PMC4832230.
[8]: Zhang H, Zhou L, Z et, al. Intermittent hypoxia aggravates non-alcoholic fatty liver disease via RIPK3-dependent necroptosis-modulated Nrf2/NFκB signaling pathway. Life Sci. 2021 Nov 15;285:119963. doi: 10.1016/j.lfs.2021.119963. Epub 2021 Sep 16. PMID: 34536498.
[9]:Xu H, Du X, et, al. The pseudokinase MLKL regulates hepatic insulin sensitivity independently of inflammation. Mol Metab. 2019 May;23:14-23. doi: 10.1016/j.molmet.2019.02.003. Epub 2019 Feb 20. PMID: 30837196; PMCID: PMC6480316.
| Cell experiment [1]: | |
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 experiment [2]: | |
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]. |
References: | |
| Cas No. | 1346546-69-7 | SDF | |
| Canonical SMILES | O=S(C1=CC=C2N=CC=C(NC3=CC=C(SC=N4)C4=C3)C2=C1)(C(C)C)=O | ||
| Formula | C19H17N3O2S2 | M.Wt | 383.49 |
| Solubility | DMSO : ≥ 100 mg/mL (260.76 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6076 mL | 13.0381 mL | 26.0763 mL |
| 5 mM | 0.5215 mL | 2.6076 mL | 5.2153 mL |
| 10 mM | 0.2608 mL | 1.3038 mL | 2.6076 mL |
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- Purity: >99.50%
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Related Biological Data
Pharmacological blockade of autophagy neutralizes the effects of RIPK1/RIPK3 inhibition. (D, H) following treatment Nec-1 (100 μM) and GSK (10 μM). Representative images and percentages of LC3-II, P62, active-cathepsin D
Combination of Nec-1 (10μM) and GSK (1μM) (GLPBIO, USA) down-regulates the levels of RIPK1, ser166-p-RIPK1, RIPK3, ser232-p-RIPK3, alleviates cell death and restores autophagic flux of CFs.
Cell Death & Disease 13.2 (2022): 1-11. PMID: 35165268 IF: 8.469 -
Related Biological Data
GSK0 872 pretreatment inhibited necroptosis in cardiomyocytes. (A) RIPK3 was immunofluorescence stained by Alexa Fluor 488 (Green)-conjugated IgG. The nuclei were stained by DAPI (Blue).
In addition, cardiomyocytes were transfected with RIPK3 siRNA or RIPK3 inhibitor GSK 872 (10µM, GlpBio,Montclair, CA, USA) for pretreatment for 4h followed by AGEs stimulation for 24h.
J Exp Clin Canc Res 41.1 (2022): 1-17. PMID: 35805993 IF: 5.5999 -
Related Biological Data
SARS-CoV-2 E protein induced pyroptosis-like death in THP-1 cells. (A)The release of LDH to the supernatant and the cell viability were detected respectively using the commercial kits.
THP-1 cells were pretreated with different cell death inhibitors ZVAD (50μm), Fer-1 (3μm), Necro (3μm), and GSK-872 (GLPBIO, USA, 3μm) for 1h, followed by 1μg/mL of E protein stimulation for 4h.
Biochemistry and Cell Biology (2023). PMID: 36927169 IF: 2.8997
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