SP600125

Inhibition of JNK with SP600125 reversed PPD-induced apoptosis, indicating that JNK signaling plays a critical role...Our findings revealed that PPD exerts potent anti-melanoma effects by directly targeting MLK3 and activating the MLK3-JNK signaling pathway, leading to apoptosis. These results provide novel insights into the molecular mechanism of PPD and suggest its potential as a therapeutic agent for melanoma treatment.

Pharmacological modulators (SC79, SP600125) were used to verify pathway roles. UA sensitizes BCa to GEM chemotherapy by promoting apoptosis, mediated through PI3K/AKT inactivation and JNK activation. These findings highlight UA as a promising adjunct to GEM therapy, warranting further clinical exploration.

Treatment with SP600125 (JNK inhibitor) or SB203580 (p38 MAPK inhibitor) effectively recused JNK and p38 activation. Both inhibitors also reduced the apoptotic cell population, which was upregulated by USP42 silencing. These findings highlight USP42 promotes breast cancer progression by reducing JNK and p38 activation and inhibiting apoptosis, suggesting its potential as a therapeutic target in breast cancer treatment.

Further ranking according to their blood-brain barrier permeability, as well as structural and transcriptomic similarities to known anti-GBM drugs, revealed SP600125, vemurafenib, FG-7142, dibenzoylmethane, and phensuximide as the most promising for GMT inhibition. In vitro validation showed that SP600125, which is most closely associated with GMT-related hub genes, effectively inhibited TGF-β1- and chemical hypoxia-induced GMT in U87 GBM cells by reducing morphological changes, migration, vasculogenic mimicry, and mesenchymal marker expression. These results clearly demonstrate the applicability of connectivity mapping as a powerful tool to accelerate the discovery of effective GMT-targeting therapies for GBM and significantly expand our understanding of the antitumor potential of SP600125.

Elp3 may be involved in GC progression by activating the JNK/MAPK pathway through histone acetylation.

A specific pharmacological inhibitor of JNK (SP600125) significantly attenuated CSE-induced RUNX2 and Galectin-3 expression, and also reversed CSE-driven EMT marker alterations, suppressed transcriptional EMT perturbations, and reduced proinflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α). In conclusion, this study identifies that ROS/JNK/RUNX2/Gal-3 axis drives CS-induced oncogenic plasticity, suggesting that targeted inhibition of this pathway could be an effective strategy for mitigating CS-related LC progression.

HYXPT exerts its therapeutic effects on PLGC by regulating the JNK/c-Jun/Slug signaling pathway, thereby inhibiting EMT during PLGC progression.

This study aimed to investigate the effects of DAPA on nicotine (NIC)-induced apoptosis in human kidney proximal tubular epithelial (HK-2) cells.MethodsHK-2 cells were treated with NIC, DAPA or selective mitogen-activated protein kinase (MAPK) inhibitors (SP600125 and SB203580). Dapagliflozin and MAPK attenuations regulate the expression of oxidant and antioxidant proteins, reducing intracellular ROS and MitoSOX overproduction and thereby alleviating mitochondrial dysfunction and ER stress. Both agents also significantly reduced pro-inflammatory cytokine levels, including TNF-α and IL-1β.ConclusionsThese findings suggest that DAPA protects HK-2 cells from NIC-induced apoptosis by modulating the ASK1/p38/JNK MAPK signalling pathway, reducing oxidative stress and alleviating inflammation.

This study was performed to investigate the anticancer activity of cynaropicrin (a natural product) in CRC HCT116 cells and an oxaliplatin (Ox)-resistant HCT116 strain (HCT116-OxR)...In addition, treatment with the kinase-specific inhibitors SP600125 and SB203580 confirmed that this apoptosis was mediated by JNK and p38 MAPK. Flow cytometry analysis using the CellROX™ kit showed cynaropicrin increased reactive oxygen species (ROS) levels, and N-acetylcysteine pretreatment confirmed ROS mediated the cytotoxicity of cynaropicrin...In conclusion, cynaropicrin demonstrated anticancer activity against CRC cells by elevating ROS levels, activating JNK and p38 MAPK, and inducing cell cycle arrest leading to apoptosis. Further studies are warranted to evaluate the therapeutic potential of cynaropicrin in CRC.

Notably, SP600125 and PD98059 contributed to the inhibition of EMT and EGFR/JNK/ERK pathway-related proteins by apatinib in sorafenib-resistant HCC. Apatinib potentially hindered the progression of sorafenib-resistant HCC by suppressing both EMT and the EGFR/JNK/ERK pathway.

Specifically, overlapping areas between the panels showing the "Lep+SP600125" and "Lep+PD098059" groups in SKOV3 cells have been detected within Figure 4...As a result, the article is retracted. The authors have been informed of the retraction decision and disagree with it.

We assessed the effects of inhibitors of epidermal growth factor receptor (EGFR) (Tyr - tyrphostin AG 1478) and c-Jun N-terminal kinase (JNK) (SP - SP600125, Lico - licochalcone A), as well as protein kinase C (PKC) activator (TPA) and inhibitor (Rot - rottlerin). More importantly, the sensitizing effects of the inhibitors were linked to increased intracellular HY accumulation, indicating reduced BCRP efflux activity. While the exact mechanisms behind these effects require further investigation, our findings suggest that targeting BCRP and associated signaling pathways could enhance PDT outcomes in cancer treatment.