SB202190

The mice in the anti-p38MAPK group and the anti-p38MAPK + LV-OPN-0423 group were then given SB202190 (this is an inhibitor of p38MAPK) for 4 weeks, and the mice in each group were injected with corresponding lentivirus diluent once a week for 8 weeks...The OPN level promoted the expression of p38MAPK and p-p38MAPK. These results suggested that OPN could regulate Em's growth and metastasis through the p38MAPK signalling pathway in host hepatocytes, providing evidence that OPN and p38MAPK may be novel molecular targets for treating alveolar echinococcosis.

Our model showed that both corneal epithelium and fibroblasts synthesize their own estrogen, and β-estradiol treatment via p38 MAP kinase pathway regulates MMP2-mediated collagen fiber degradation. p38 MAP kinase inhibitor SB202190 significantly reduced β-estradiol-induced MMP activity and collagen breakdown, as well as cytokine regulation suggesting a potential therapeutic approach.

The Nrf2/HMOX1 pathway is a significant contributor to cisplatin resistance in NSCLC. Targeting HO-1 with SB 202190 and NDGA presents a promising strategy to overcome resistance and improve chemotherapy outcomes.

A screen for modulators of SB202190-induced vacuolation revealed molecules including multi-kinase inhibitor sorafenib as inhibitors of vacuolation and sorafenib co-treatment enhanced cytotoxicity of SB202190. To identify the factors determining the cell-type specificity of vacuolation induced by SB-compounds and VE-821, we compared the transcriptomics data from vacuole-forming and non-vacuole-forming cancer cell lines and identified a gene expression signature that may define sensitivity of cells to these small-molecules. Further analyses using small molecule tools and the gene signature discovered here, could reveal novel mechanisms regulating this interesting anti-cancer phenotype.

Experimental groups were divided based on the different treatments during resuscitation as follows: (1) hemorrhage: adult male CD-1 mice were subjected to hemorrhage at a mean arterial blood pressure of 35-45 mm Hg for 60 minutes, followed by resuscitation with shed blood and lactated Ringer's solution (n = 13); (2) hemorrhage + irisin: receiving irisin (5 μg/kg; n = 13); (3) hemorrhage + irisin + PI3K inhibitor: receiving both Ly294002 (1 mg/kg, i.v.) and irisin (n = 6); and (4) hemorrhage + irisin + p38 inhibitor: receiving SB202190 (1 mg/kg, i.v.) and irisin (n = 6). SIGNIFICANCE STATEMENT: This study has identified a critical pathway in the regulation of trauma/hemorrhage by using a preclinical trauma model, in which irisin, as a hormone factor, stimulates PI3K and p38 pathways to induce protection against traumatic conditions. The study holds promise for developing a new therapeutic strategy to target irisin and its pathways related to PI3K and p38 to treat trauma and its comorbidities to reduce mortality for clinical implications.

Employing the standard MTT assay, every target compound's in vitro antiproliferative efficacy was evaluated in comparison with doxorubicin against both normal WI-38 cells and various cancer cell lines...The in vitro enzyme assay showed that the new analogues had a better ability to inhibit p38α MAPK kinase than SB 202190 (IC50s = 0.18 ± 0.02, 0.23 ± 0.05, 0.31 ± 0.04, and 0.27 ± 0.06 μM, respectively)...Based on the molecular docking study, candidates 6, 8a, and 8b all fit well within p38α MAPK kinase, with energy scores of -10.88, -11.28, and -10.96 kcal mol-1, respectively. Based on the in silico computer examination of physico-chemical and ADMET properties, the latter analogues seem to be promising candidates for further development and optimization in research.

The IL-22-mediated changes in cell proliferation, cycle progression, and protein expression can be effectively inhibited by the ERK1/2 inhibitor U0126 and the p38 inhibitor SB202190...Our findings suggest that IL-22 promotes endometrial carcinoma cell proliferation and G1/S phase progression by activating ERK1/2 and p38 signaling. Therefore, IL-22 may represent a potential therapeutic target for the treatment of endometrial carcinoma.

Latency establishment was mimicked by culturing HSV-1 infected ND7/23 cells in the presence of acyclovir (ACV) for 3 days...There were no changes in the pharmacological and biophysical properties of sodium currents promoted by TNF-α, including sensitivity to tetrodotoxin and the current-voltage relationship...Inhibition of p38 signaling with SB203580 or SB202190 eliminates the stimulatory effect of TNF-α on sodium currents. These results indicate that TNF-α signaling in sensory neurons during latency establishment upregulates the expression of voltage-gated Na+ channels in order to maintain the transmission of pain information.

Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. Real-time PCR analysis demonstrated that components of these pathways including IL1β, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future.

We design a growth factor-reduced culture medium containing FGF10, A83-01 (TGF-β type I receptor inhibitor), SB202190 (p38 MAPK inhibitor), gastrin, and nicotinamide. Using this medium, we can maintain tumor features in long-term CRCO cultivation, as evidenced by histopathology, genetic stability, tumorigenicity, and response of clinical treatments. Our findings offer a reliable and economical strategy for CRCO culture, facilitating the utilization of organoids in colorectal cancer research and treatment.

p38 mitogen-activated protein kinases (MAPKs) participate in autophagic signaling; and previous reports suggest that pyridinyl imidazole p38 MAPK inhibitors, including SB203580 and SB202190, induce cell death in some cancer cell-types through unrestrained autophagy. The rate of vacuole dissolution (i.e., LEL fission), following the removal of apilimod, was also significantly reduced in cells treated with BIRB-796, a structurally unrelated p38 MAPK inhibitor. Thus, our studies indicate that pyridinyl imidazole p38 MAPK inhibitors induce cytoplasmic vacuolation through the combined inhibition of both PIKfyve and p38 MAPKs, and more generally, that p38 MAPKs act epistatically to PIKfyve, most likely to promote LEL fission.

These results suggest that TSG-6 expression in ASCs can be regulated by high concentrations of pro-inflammatory cytokines in vitro and in vivo, and that A83-01 and SB202190 can reduce the expression of immunomodulators in ASCs. Therefore, our data suggest that co-treatment of ASCs with TGF-β or p38 inhibitors is not adequate to modulate inflammation.