GSK-872 is an inhibitor of RIPK3 that binds to the RIP3 kinase domain with an IC50 of 1.8 nM, and it inhibits kinase activity with an IC50 of 1.3 nM. GSK-872 reduces RIPK3-mediated necroptotic cell death, subsequent cytoplasmic translocation, and expression of HMGB1, improving early brain injury-related cerebral edema and neurological deficits[1][2][3]. Within a concentration range of 0.01-3 μM, GSK-872 blocks TNF-induced necroptotic cell death in human HT-29 cells in a concentration-dependent manner over 24 hours[1].
GSK-872 细胞实验
Cell Line
Concentration
Treated Time
Description
References
hepG2 cells
5 μM
24 h
GSK-872 can restore cell death caused by knockdown of HABON
Cell Death Discov. 2022 Apr 6;8(1):171.
hNPCs
5 μM
To study the mechanism of ZIKV-induced cell death, GSK872 was used to inhibit necroptosis
Cells. 2020 Nov 16;9(11):2487.
SMMC-7721 cells
5 μM
24 h
GSK-872 can restore cell death caused by knockdown of HABON
Cell Death Discov. 2022 Apr 6;8(1):171.
Huh7 cells
5 μM
24 h
GSK-872 can restore cell death caused by knockdown of HABON
Cell Death Discov. 2022 Apr 6;8(1):171.
T24 resistant cells
2 µM
24 h
Inhibited RIP3 phosphorylation and reduced cell death caused by shikonin or its combination with cisplatin
Int J Biol Sci. 2018 Oct 20;14(13):1883-1891.
RAW264.7 cells
5 µM
Inhibition of RIPK3 kinase activity reduced the accumulation of autophagic flux
Clin Transl Med. 2023 Jul;13(7):e1334.
NZM2328 mouse podocyte cell line
3µM
1 h
GSK872 inhibited the phosphorylation of RIP3 and MLKL, and blocked the activation of the NLRP3 inflammasome
J Autoimmun. 2019 Sep;103:102286.
RAW264.7 cells
3 µM
24 h
GSK872 inhibited the RIP3 signaling pathway, reduced the expression of inflammatory cytokines and chemokines, and significantly decreased the apoptosis rate of RAW264.7 cells.
Front Immunol. 2021 Mar 25;12:624360.
GSK-872 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Sepsis model
Intraperitoneal injection
3 mg/kg
Administered at 0, 12, 24, 48, and 72 hours post-CLP
Inhibition of necroptotic signaling ameliorated sepsis-induced multiple organ dysfunction and systemic inflammation
Clin Transl Med. 2023 Jul;13(7):e1334.
Mouse
MRL/lpr mice
Intraperitoneal injection
1mg/kg
Once daily for 2 weeks
GSK872 significantly reduced the expression of p-RIP3 and p-MLKL in the kidneys, inhibited the activation of the NLRP3 inflammasome, and improved nephritis symptoms
J Autoimmun. 2019 Sep;103:102286.
Mice
LPS-induced systemic inflammation model
Intraperitoneal injection
2 mg/kg
Single dose, lasting 72 hours
GSK872 suppressed RIP3-mediated necroptosis and restored Kir4.1 protein expression, alleviating LPS-induced brain endothelial cell damage and increased neuronal excitability.
J Neuroinflammation. 2022 Feb 2;19(1):29
Mice
DSS-Con A induced autoimmune hepatitis model
Intraperitoneal injection
1 mg/kg
Single dose, lasting 1 hour
GSK872 significantly inhibited the activation of the RIP3 signaling pathway, reduced the activation and infiltration of liver macrophages, and alleviated liver inflammation and injury.
Front Immunol. 2021 Mar 25;12:624360.
GSK-872 动物研究
Animal study
Administered intracerebroventricularly at 25 mM, GSK-872 alleviates cerebral edema and improves neurological functions following subarachnoid hemorrhage (SAH), and reduces the number of necrotic cells. GSK-872 also lowers the protein levels of RIPK3 and MLKL, as well as the cytoplasmic translocation and expression of the pro-inflammatory protein HMGB1[3].
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