Notably, claudin-11, an oligodendrocyte-specific, tight junction protein, was identified as a novel phospho-target that was highly reduced upon DJNKI-1 treatment. Together, these findings highlight potential molecular markers of anxiolytic response and suggest synaptic and metabolic interplay in mood regulation.

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.

These findings indicate that γT3 and δT3 inhibit HCC2998 cell proliferation by activating the DDR pathway, highlighting their potential as therapeutic agents to overcome cell cycle arrest resistance in CRC. This study provides critical insights into the molecular actions of γT3 and δT3, supporting their further investigation as promising candidates for CRC intervention.

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.

These findings suggest that CEACAM7 promotes oral cancer metastasis by regulating CD317 through the p-JNK and p-Src pathways. CEACAM7 and CD317 may therefore represent potential therapeutic targets for the treatment of metastatic oral cancer.

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

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.

The IKBKE-inhibitor Amlexanox, clinically utilized for aphthous ulcers, as well as the MAPK8 inhibitor JNK-IN-8, reinstalled the DCIS-like phenotype of breast cancer cells on high matrix stiffness. This suggests that IKBKE and/or MAPK8 inhibitors could enhance the arsenal of treatments to prevent or treat breast cancer.