SB202190

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.

We investigated the growth inhibitory, cisplatin-sensitizing, and pro-apoptotic effects of p38 MAPK inhibition in cisplatin-resistant (SCC-25) and -sensitive (UPCI-SCC090) HNSCC cell lines, using two specific p38 MAPK inhibitors, SB202190 and ralimetinib. In accordance, p-p38 inhibition led to sensitization of pEMT cells to cisplatin-induced cell death; moreover, p-p38 inhibitor treatment cycles significantly decreased the viability of cisplatin-surviving cells. In conclusion, clinically relevant p38 inhibitors might be effective for RCT-resistant pEMT cells in HNSCC patients.

Additionally, QYLGT-activated c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-kappa B (NF-κB), and the related inhibitors, including SP600125, PD184352, SB202190, and Bay11-7082, were used to confirm which signaling was involved in QYLGT-induced apoptosis. Moreover, only Bay11-7082, the NF-κB inhibitor, could suppress QYLGT-induced the release of cytokeratin 18 fragments from OEC-M1 cells. QYLGT induced apoptosis in OEC-M1 cells via the NF-κB pathway.

MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.

Using high-throughput virtual screening, 1909 geometrically similar analogs of known inhibitors were generated, primarily using BIRB796, SB202190, ANP, CHEBI: 620708, and CHEBI: 524699...Notably, Lead '1' (3-deazaadenosine) exhibited favorable root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) within the acceptable range of pharmacological properties. Thus, 3-deazaadenosine and its mimetic might be promising new directions for developing a novel class of antagonists for breast cancer treatment.

Nitric oxide (NO) is a crucial factor in regulating neuronal development. Survival and cell viability increased in the SB202190 and SNP co-treated group. Taken together, our results suggested that p38 is involved in the cell survival of NSCs, regulated by NO.

SB202190 was a more effective inhibitor of BRAF-mutated organoid growth in the long term than the specific BRAF inhibitors Dabrafenib and PLX8394. Overall, SB202190 can predict BRAF-activating mutations in patient-derived organoids, as well as allowing for the identification of new BRAF variants, preceding and enforcing NGS data.

The activity of mitogen-activated protein kinase (MAPK) was elevated in the tumor cells treated with E, and E-stimulated secretion of LPL was suppressed by the MAPK kinase 1/2 inhibitor PD98059, extracellular signal-regulated kinase (ERK) 1/2 inhibitor FR180204, p38 MAPK inhibitor SB202190, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. In addition, the effect of E on active LPL secretion was markedly suppressed by an inhibitor of mammalian target of rapamycin complex (mTORC) 1 and 2, KU0063794, but not by the mTORC1 inhibitor, rapamycin. Furthermore, a small interfering RNA (siRNA)-mediated decrease in the expression of rapamycin-insensitive companion of mTOR (Rictor), a pivotal component of mTORC2, suppressed the secretion of LPL by E. Stimulatory secretion of LPL by E from the tumor cells is closely associated with activation of mTORC2 rather than mTORC1, possibly via the MAPK cascade.

Extensive molecular analyses in the cellular and in vivo models revealed that the p38α kinase inhibitors, SB202190 and ralimetinib, affect c-MYC protein levels. Ralimetinib also exhibited a synthetic lethality effect when used in combination with the MEK1 inhibitor trametinib. Overall, our findings identify p38α as a promising therapeutic target, acting directly on c-MYC, with potential implications for countering c-MYC-mediated CRC proliferation, metastatic dissemination, and chemoresistance.

After confirming the phenotypic characterization of KG1a and HL60 cells using flow cytometry and transcriptomic array analyses, cell treatment with the NF-κB inhibitor IKKVII resulted in a complete induction of apoptosis, and a few p38 MAPK inhibitor SB202190-treated cells underwent apoptosis. No change in the apoptosis status was observed in the ROS scavenger N-acetylcysteine-treated cells...The miR-328-3p is known for the enhancement of cancer cell chemosensitivity and apoptosis induction, and the downregulation of miR-210-5p is found in AML patients in complete remission. In conclusion, we highlighted the key role of the p38 MAPK survival pathway in the chemoresistance capacity of the AML stem cells and potentially involved miRNAs, which may pave the way for the development of a new therapeutic strategy targeting survival signaling proteins and reduce the rate of AML relapse.

The activation of the PERK-Ca-calcineurin axis by SB202190 positively affects TFEB activity to increase ALP in neuroblastoma cells. Collectively, our study reveals a novel physiological mechanism underlying ALP activation, dependent on PERK activation, for ameliorating amyloidogenesis in neurodegenerative diseases.

GRP78 transcription was more greatly induced by insulin in the presence of SB202190, a specific p38-MAPK inhibitor. Transcription of GRP94 was also induced, but only after several hours. Calcimycin (A23187) and anisomycin were used to induce endoplasmic reticulum (ER)/cellular stress, and both induced GRP78 and GRP94 transcription.

Attenuation of PD-L1 expression was examined by qRT-PCR in HLF and Hep3B pretreated with BAY11-7082 (NF-кB inhibitor), U0126 (MEK 1/2 inhibitor), SB202190 (p38 MAPK inhibitor), SP600125 (JNK inhibitor) or Ruxolitinib (JAK inhibitor), and stimulated with IFN-γ and IL-1β. Our data demonstrated the synergic effect of IFN-γ and IL-1β on PD-L1 expression in HCC cells. We found that the significant contribution of IRF-1 and the STAT signaling to induction of PD-L1.

Attenuation of PD-L1 expression was examined by qRT-PCR in HLF and Hep3B pretreated with BAY11-7082 (NF-кB inhibitor), U0126 (MEK 1/2 inhibitor), SB202190 (p38 MAPK inhibitor), SP600125 (JNK inhibitor) or Ruxolitinib (JAK inhibitor), and stimulated with IFN-γ and IL-1β. Our data demonstrated the synergic effect of IFN-γ and IL-1β on PD-L1 expression in HCC cells. We found that the significant contribution of IRF-1 and the STAT signaling to induction of PD-L1.

Attenuation of PD-L1 expression was examined by qRT-PCR in HLF and Hep3B pretreated with BAY11-7082 (NF-кB inhibitor), U0126 (MEK 1/2 inhibitor), SB202190 (p38 MAPK inhibitor), SP600125 (JNK inhibitor) or Ruxolitinib (JAK inhibitor), and stimulated with IFN-γ and IL-1β. Our data demonstrated the synergic effect of IFN-γ and IL-1β on PD-L1 expression in HCC cells. We found that the significant contribution of IRF-1 and the STAT signaling to induction of PD-L1.

The addition of p38 inhibitor, Doramapimod or SB202190, to IL-7 and IL-15 culture largely increased the capacity of T cells in the proliferation with enrichment of the naïve-like subsets and expression of CD62L...Such findings were also validated in the melanoma-associated antigen recognized by T cells (MART-1) specific T cell receptor (TCR) engineered T cells, which were expanded in Doramapimod and IL-7 + IL-15 added media. In conclusion, we have established and optimized a protocol with the combination of p38 inhibitor, IL-7 and IL-15, rather than IL-2, for the generation of functionally enhanced T cells applicable for ACT.

However, the resulting increase in extracellular dopamine, but not norepinephrine, could be suppressed by p38 inhibitor SB202190. Our results suggest that both extracellular dopamine and norepinephrine homeostasis could be regulated by ErbB4 in human catecholaminergic cells, and ErbB4 may regulate extracellular dopamine, but not norepinephrine, through the p38 MAPK signaling pathway, thus indicating different regulatory pathways of dopamine and norepinephrine by ErbB4 in catecholaminergic neurons.

Cells cultured on mechanically stiff substrates had enhanced PRB activation via a mechanism that required MEK 1/2 and AKAP13/RhoA/ROCK signaling pathways. These studies provide a framework to explore the mechanisms by which mechanical stiffness affects progesterone receptor activation.

This study is the first to demonstrate that activation of C/EBPβ by p38β MAPK may contribute to tumorigenesis and progression of Activin A-induced leiomyoma. Specific p38β inhibition may represent a novel and promising intervention for leiomyoma.

Furthermore, SKOV3 spheroid invasion was blocked by p38 inhibition with SB202190, but not by MEK inhibition with U0126; whereas TOV112D spheroid invasion was reduced by MEK inhibition, but not by p38 inhibition. These results indicate that nicotine can suppress spheroid invasion and compaction as well as proliferation in SKOV3 and TOV112D OC cells; and p38 and ERK MAPK signaling pathways are important mediators of these responses.

Here, we identified pyridinyl imidazole compounds SB202190, SB203580, and SB590885 as dual inhibitors of critical proliferative pathways in human melanoma cells bearing the V600E activating mutation of BRAF kinase. We found that the drugs simultaneously disrupt the BRAF V600E-driven extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) activity and the mechanistic target of rapamycin complex 1 (mTORC1) signaling in melanoma cells...The induced disruption of the endolysosomal pathway not only disrupts mTORC1 signaling, but also renders melanoma cells sensitive to endoplasmic reticulum (ER) stress. Our findings identify new activities of pharmacologically relevant small molecule compounds and provide a biological rationale for the development of anti-melanoma therapeutics based on the pyridinyl imidazole core.

Blockade of autophagy with 3-methyladenine (3-MA) and chloroquine (CQ), two autophagy inhibitors, potentiated the OMEO-induced apoptotic cell death...Pharmacological inhibition of p38 MAPK by the p38 inhibitors SB 202190 and SB 203580 not only significantly decreased apoptotic cell death, but also reduced the autophagy level in OMEO treated HT-29 cells...Our findings suggest that OMEO inhibits colon cancer through p38 MAPK-mediated protective autophagy and apoptosis associated with caspase-dependent cleavage of p70S6K. To the best of our knowledge, this study is the first to report on the implications of the p38 MAPK signaling pathway in targeting p70S6K to caspase cleavage.

1,8-Cineole induces G0/G1 arrest and senescence in HepG2 cells through oxidative stress and MAPK, AMPK, and Akt/mTOR pathways, and sensitizes cells to anti-senescence drugs, suggesting that 1,8-cineole has potential as an antineoplastic and adjuvant compound in combination with anti-senescence drugs in HCC therapy.