Ponicidin

Ponicidin (Rubescensine B) is an orally active RIPK1 inhibitor with a K_d value of 135 nM. Ponicidin inhibits the JAK2/STAT3 pathway to induce apoptosis, activates the PI3K/Akt pathway, upregulates SIRT1 expression, alleviates oxidative stress, suppresses inflammatory responses and necroptosis, and blocks cell cycle progression. Ponicidin induces ROS production to exert antiproliferative and antiviral effects, while also improving cognitive function and reducing Aβ plaque deposition. Ponicidin can be used in studies related to hepatocellular carcinoma, Alzheimer's disease, and gastric cancer^[1][2][3][4]. IC50 & Target:Apoptosis^[1] In Vitro:Ponicidin (5-40 μM; 24-72 h) inhibits the viability of QGY-7701 and HepG-2 human hepatocellular carcinoma cells in a dose- and time-dependent manner, with treatment at 40 μM for 72 h reducing cell viability to 9.3% (QGY-7701) and 12.7% (HepG-2), respectively^[1].
Ponicidin (40 μM; 48-72 h) downregulates the mRNA and protein expression of Survivin and Bcl-2, while upregulating the mRNA and protein expression of Bax, in QGY-7701 and HepG-2 human hepatocellular carcinoma cells^[1].
Ponicidin (1-50 μM; 24 h) shows no significant cytotoxicity against HT-22 mouse hippocampal neuronal cells, while Ponicidin (10 μM; 2 h pre-incubation) significantly restores the cell viability reduced by Aβ_1-42 exposure^[2].
Ponicidin (10 μM; pre-incubated for 2 h) significantly alleviates Aβ_1-42-induced neuroinflammation in HT-22 mouse hippocampal neuron cells by downregulating pro-inflammatory cytokines (TNF-α, IL-1β) and upregulating the anti-inflammatory factor IL-10^[2].
Ponicidin (10 μM; preincubated for 2 h) significantly reduces Aβ_1-42-induced intracellular ROS production and oxidative stress in HT-22 mouse hippocampal neuronal cells by decreasing lipid peroxidation levels and restoring antioxidant enzyme activity^[2].
Ponicidin (10 μM; 2 h pre-incubation) significantly upregulates the expression of SIRT1 in Aβ_1-42-treated HT-22 mouse hippocampal neurons and modulates the activation of the PI3K/Akt pathway, while SIRT1 inhibitors reverse these effects^[2].
Ponicidin (10 μM; 2 h pre-incubation) significantly enhances the expression of BDNF and NGF in Aβ_1-42-treated HT-22 mouse hippocampal neuron cells via a SIRT1-mediated mechanism^[2].
Ponicidin (10-50 μM; 48 h) induces dose-dependent apoptosis in human gastric cancer MKN28 cells, with the proportion of early apoptotic cells reaching 59.03% at the concentration of 50 μM^[3].
Ponicidin (10-50 μM; 48 h) induces dose-dependent G0-G1 cell cycle arrest in human gastric cancer MKN28 cells, increasing the proportion of G0-G1 phase cells to 60.68% at a concentration of 50 μM. It also reduces the proportions of cells in S phase and G2-M phase^[3].
Ponicidin (10-50 μM; 1-48 h) induces time- and dose-dependent activation of caspase-3 in human gastric cancer MKN28 cells, with its activity reaching 28.76% at 50 μM for 48 h^[3].
Ponicidin (1.56-100 μM; 8 h) exhibits a CC₅₀ of 59.360 μM in BV2 microglial cells, and shows low cytotoxicity at a concentration of 5 μM^[4].
Ponicidin (5 μM; 8.5 h) inhibits Z-VAD (LZ) (HY-164388)-induced secretion of TNF-α (IC₅₀ = 3.56 μM) and IL-6 (IC₅₀ = 2.635 μM) in BV2 microglia, with significant inhibitory effects observed at a concentration of 5 μM^[4].
Ponicidin (5 μM; 8.5 h) inhibits TZ-induced LDH release and protects HT22 neuronal cells from necroptosis-associated membrane damage^[4].
Ponicidin (5 μM; 8.5 h) inhibits neuronal necroptosis by blocking the RIPK1-RIPK3-MLKL signaling cascade, and reduces the phosphorylation levels of RIPK1, RIPK3 and MLKL in TZ-stimulated HT22 neuronal cells^[4]. In Vivo:Ponicidin (5-10 mg/kg/day; oral; daily; 30 days) significantly improves cognitive function, reduces Aβ plaque deposition, and inhibits neuroinflammation and necroptosis in 5×FAD transgenic mice^[4].