U0126 / Promega 
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  • ||||||||||  Adomet (S-adenosyl-L-methionine) / Abbott, U0126 / Promega
    Preclinical, Journal:  MAT2A/2B promote porcine intramuscular preadipocyte proliferation through ERK signaling pathway. (Pubmed Central) -  Feb 8, 2020   
    Moreover, the inhibitory effect of U0126 (a specific ERK1/2 inhibitor) on the ERK1/2 activities was partially recovered by overexpression of MAT2A and MAT2B in porcine intramuscular preadipocytes. Taken together, our findings suggested that MAT2A and MAT2B promote porcine preadipocyte proliferation by ERK1/2 signaling pathway.
  • ||||||||||  U0126 / Promega
    Journal:  C-kit signaling promotes human pre-implantation 3PN embryonic development and blastocyst formation. (Pubmed Central) -  Feb 7, 2020   
    The present study firstly revealed that c-kit signaling might promote the human pre-implantation embryonic development and blastocyst formation by up-regulating the expression of ETV5 via MEK/ERK pathway. Our findings provide a new idea for optimizing the in vitro embryo culture condition during ART program, which is beneficial to obtain high quality embryos for infertile patients.
  • ||||||||||  U0126 / Promega
    Journal:  Astrocytes and Microglia Are Resistant to NAD-Mediated Cell Death Along the ARTC2/P2X7 Axis. (Pubmed Central) -  Feb 6, 2020   
    We found that astrocytes and microglia strongly upregulate cell surface levels of ARTC2.1 and ADP-ribosylation of cell surface proteins in response to treatment with lipopolysaccharide (LPS) and the mitogen-activated protein kinase kinase (MEK) 1 and 2 inhibitor U0126, but do not respond to extracellular NAD with P2X7 activation and induction of cell death. Furthermore, we found that astrocytes and microglia preferentially express the ADP-ribosylation-insensitive P2X7a splice variant, likely accounting for the resistance of these cells to NICD.
  • ||||||||||  U0126 / Promega
    Journal:  Ginkgo Biloba Extract Inhibits Metastasis and ERK/Nuclear Factor kappa B (NF-κB) Signaling Pathway in Gastric Cancer. (Pubmed Central) -  Feb 1, 2020   
    Furthermore, the migration and invasiveness were weakened and the protein levels of p-ERK1/2, NF-kappaB P65, NF-kappaB p-P65, and MMP2 were decreased by EGb761 or U0126 (an inhibitor of ERK signaling pathway) exposure in gastric cancer cells...Results of immunohistochemistry indicated that the expression of ERK1/2, NF-kappaB P65 and MMP2 were decreased by EGb761 in the tumor tissues. CONCLUSIONS EGb761 plays a vital role in the suppression of metastasis and ERK/NF-kappaB signaling pathway in gastric cancer.
  • ||||||||||  bortezomib / Generic mfg., Farydak (panobinostat) / Novartis, U0126 / Promega
    Journal:  SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells. (Pubmed Central) -  Jan 29, 2020   
    We identified Panobinostat, an FDA approved pan-HDAC inhibitor, could elevate and restore SOX7 expression in SOX7 silenced lung cancer cells. Taken together, these data revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling.
  • ||||||||||  U0126 / Promega
    LYSOPHSOPHATIDIC ACID RECEPTOR 5 ENHANCES INTESTINAL EPITHELIAL BARRIER BY REGUATING CLAUDIN-4 () -  Jan 28, 2020 - Abstract #DDW2020DDW_2355;    
    To determine the signaling pathway regulating claudin-4 and epithelial barrier function, Caco-2bbe cells expression HA-LPA5R were treated with U0126, Gö6983 or Y27632...These results suggest that LPA5R enhances intestinal barrier function in part through increasing claudin-4. We are currently investigating whether the epidermal growth factor receptor is involved in the transcriptional regulation of claudin-4 and the role of Rac1 in occludin regulation
  • ||||||||||  sirolimus / Generic mfg.
    Clinical, Journal:  Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis. (Pubmed Central) -  Jan 25, 2020   
    Our studies using cells from KLA patient lesions demonstrate that these cells are highly proliferative and the PI3K-AKT-mTOR and MAPK pathways are promising therapeutic targets. Development and clinical trials of PI3K, AKT, and MAPK inhibitors for cancer treatment and the data in this study lend support for early clinical trials assessing the efficacy of these inhibitors in KLA patients.
  • ||||||||||  U0126 / Promega
    Journal:  Resveratrol inhibits Erk1/2-mediated adhesion of cancer cells via activating PP2A-PTEN signaling network. (Pubmed Central) -  Jan 21, 2020   
    Inhibition of Erk1/2 with U0126, knockdown of Erk1/2, or overexpression of dominant-negative mitogen-activated protein kinase kinase 1 (MKK1) strengthened resveratrol's inhibition of the basal or IGF-1-stimulated of Erk1/2 phosphorylation and cell adhesion, whereas ectopic expression of constitutively active MKK1 attenuated the inhibitory effects of resveratrol...The results indicate that resveratrol inhibits Erk1/2-mediated adhesion of cancer cells via activating PP2A-PTEN signaling network. Our data highlight that resveratrol has a great potential in the prevention of cancer cell adhesion.
  • ||||||||||  U0126 / Promega
    Preclinical, Journal:  Intermedin in Paraventricular Nucleus Attenuates Ang II-Induced Sympathoexcitation through the Inhibition of NADPH Oxidase-Dependent ROS Generation in Obese Rats with Hypertension. (Pubmed Central) -  Jan 21, 2020   
    ERK activation inhibitor U0126 in the PVN reversed Ang II-induced enhancement of SNA, and Apo and IMD pretreatment in the PVN decreased Ang II-induced ERK activation...Moreover, IMD lowered NADPH oxidase activity and ROS level in the PVN; reduced the protein expressions of AT1R and NADPH oxidase subunits NOX2 and NOX4, and ERK activation in the PVN; and decreased Ang II levels-inducing sympathetic overactivation. These results indicated that IMD via AM receptors in the PVN attenuates SNA and hypertension, and decreases Ang II-induced enhancement of SNA through the inhibition of NADPH oxidase activity and ERK activation.
  • ||||||||||  U0126 / Promega
    Journal:  TNF-alpha inhibits pregnancy-adapted Ca signaling in uterine artery endothelial cells. (Pubmed Central) -  Jan 19, 2020   
    Here we show TNF-alpha, commonly increased in PE subjects, inhibits Cx43 function and Ca bursts in pregnancy-derived ovine uterine artery endothelial cells (P-UAEC) via Src and MEK/ERK phosphorylation of Cx43, and this can be reversed by PP2 or U0126...(3) Treatment of HUV Endo from PE subjects with PP2 alone can rescue bursting and NO output. We conclude TNF-alpha acts via Src more than MEK/ERK to inhibit GJ Cx43 function in PE subjects, and CLA may offer a potential therapy.
  • ||||||||||  cyclophosphamide intravenous / Generic mfg.
    Journal:  Salidroside induces anti-tumor effect in dendritic cells via ERK pathway (Pubmed Central) -  Jan 18, 2020   
    Methods Lewis lung cancer-bearing mouse model was established and treated with normal saline (NS) (0.2 mL/d), SAL [500 mg/(kg.d)] and cyclophosphamide (CTX) [10 mg/(kg.d)] in corresponding groups...After sorted with magnetic beads, cells were co-cultured with PBS, SAL (0.05 mg/mL), LPS (200 ng/mL) or SAL combined with ERK inhibitor U0126 separately for 48 hours, followed by detection of the expression of phosphorylated ERK (p-ERK) by flow cytometry...Finally, the killing ability of CTL was significantly enhanced by SAL. Conclusion SAL can inhibit the tumor growth of Lewis lung cancer-bearing mice and activate the ERK signaling pathway, thereby promoting IL-12p70 secretion in DCs and enhancing the cytotoxicity of CTL.
  • ||||||||||  U0126 / Promega
    Journal:  Phosphorylation of extracellular signal-regulated kinase 1/2 in subepidermal nerve fibers mediates hyperalgesia following diabetic peripheral neuropathy. (Pubmed Central) -  Jan 11, 2020   
    pl.) injection with a MEK inhibitor, U0126 (1,4-Diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), hyperalgesia was attenuated in a dose-responsive manner...From the results obtained in this study, it is suggested that increases of pERK1/2 in SENFs may participate in the modulation of TRPV channel-mediated neurogenic inflammation that triggers hyperalgesia in STZ-induced diabetic rats. Therefore, ERK1/2 provides a potential therapeutic target and efficient pharmacological strategies to address hyperglycemia-induced neurotoxicity.
  • ||||||||||  U0126 / Promega
    Journal:  Notch signaling regulates osteosarcoma proliferation and migration through Erk phosphorylation. (Pubmed Central) -  Jan 11, 2020   
    Using the Erk pathway inhibitor U0126, we showed that p-Erk was downregulated and the proliferation and migration of K7M2 decreased along with it...DAPT effectively inhibits osteosarcoma proliferation and metastasis in vivo and in vitro by inhibiting Erk phosphorylation. Therefore, the inhibition of Notch activation resulted the down-regulation of phosphorylation of Erk pathway can be used as potential therapeutic targets in clinical treatment to improve osteosarcoma prognosis.
  • ||||||||||  U0126 / Promega
    Preclinical, Journal:  Blockade of ERK1/2 by U0126 alleviates uric acid induced EMT and tubular cell injury in the rats with hyperuricemic nephropathy. (Pubmed Central) -  Jan 1, 2020   
    Moreover, ERK1/2 inhibition suppressed hyperuricemic injury-induced oxidative stress as indicated by decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD). Collectively, ERK1/2 inhibition-elicited renal protection is associated with inhibition of EMT through inactivation of multiple signaling pathways and matrix metalloproteinases, as well as attenuation of renal tubule injury by enhancing cellular resistance to oxidative stress.
  • ||||||||||  quercetin (LY294002) / Eli Lilly, U0126 / Promega
    Journal:  Dual inhibition of Akt and ERK signaling induces cell senescence in triple-negative breast cancer. (Pubmed Central) -  Jan 1, 2020   
    However, NCTD upregulated the level of soluble signaling factors of the senescence-associated secretory phenotype (SASP) in a NF-κB-independent manner. Collectively, these findings demonstrate that NCTD induced cell senescence and cell cycle arrest mainly by simultaneously blocking Akt and ERK signaling in TNBC, suggesting that NCTD may be used as a potential adjuvant therapy in TNBC.
  • ||||||||||  letrozole / Generic mfg., cisplatin / Generic mfg.
    Journal:  Letrozole improves the sensitivity of breast cancer cells overexpressing aromatase to cisplatin via down-regulation of FEN1. (Pubmed Central) -  Dec 23, 2019   
    These present findings suggested that SP, released from TG neurons, activated SGCs through the ERK1/2 and P38 pathways and promoted the production of IL-1β and TNF-α from SGCs, contributing to inflammatory orofacial pain associated with peripheral sensitization. Our findings clearly demonstrate that letrozole improves cisplatin sensitivity of breast cancer cells overexpressing aromatase via down-regulation of FEN1 and suggest that a combined use of letrozole and cisplatin may be a potential treatment protocol for relieving cisplatin resistance in human breast cancer.
  • ||||||||||  U0126 / Promega
    Journal:  Spred2 Regulates High Fat Diet-Induced Adipose Tissue Inflammation, and Metabolic Abnormalities in Mice. (Pubmed Central) -  Dec 23, 2019   
    Taken together, these results suggested that Spred2, in macrophages, negatively regulates high fat diet-induced obesity, adipose tissue inflammation, metabolic abnormalities, and insulin resistance by inhibiting the ERK/MAPK pathway. Thus, Spred2 represents a potential therapeutic tool for the prevention of insulin resistance and resultant metabolic syndrome.
  • ||||||||||  U0126 / Promega
    Preclinical, Journal:  Effect of porous tantalum on promoting the osteogenic differentiation of bone marrow mesenchymal stem cells in vitro through the MAPK/ERK signal pathway. (Pubmed Central) -  Dec 19, 2019   
    Our findings will highlight the therapeutic potential of HO-1 induction in GC-induced osteoporosis. Subsequently, the two groups were treated with the MAPK/ERK-specific inhibitor U0126, and then, the mRNA expression levels of osteogenic genes and protein expression levels of p-ERK in the cultures were determined by Q-PCR and Western blotting, respectively...The translational potential of this article: Our self-developed pTa material produced by three-dimensional printing combined with the chemical vapour deposition method not only retains excellent biological activity and osteoinductive ability of the original tantalum metal but also saves considerably on material costs to achieve mass production of personalised orthopaedic implants with pTa as a stent and to accelerate the wide application of pTa implants in clinical practice, which have certain profound significance.
  • ||||||||||  quercetin (LY294002) / Eli Lilly, Tamoxis (tamoxifen) / Bioprofarma, U0126 / Promega
    Journal:  Fibrauretine reduces ischemia/reperfusion injury via RISK/eNOS activation. (Pubmed Central) -  Dec 8, 2019   
    It is suggested that eNOS plays an important role in the protective effect of fibrauretine on the heart. Therefore, the results of this study show that the protective effect of fibrauretine on myocardial I/R injury is closely associated with eNOS expression, GR/ER-induced Akt phosphorylation and ERK1/2 activation.
  • ||||||||||  U0126 / Promega
    Journal:  Gain-Of-Function E76K-Mutant SHP2 Promotes Cell Proliferation, Metastasis, And Tumor Growth In Glioblastoma Through Activation Of The ERK/CREB Pathway. (Pubmed Central) -  Dec 8, 2019   
    Finally, ERK was inhibited using a mitogen-activated protein kinase/ERK kinase inhibitor (U0126) to further explore the molecular mechanism of GOF-mutant SHP2 affecting GBM cells...Furthermore, following inhibition of ERK in the GOF-SHP2 mutant group, the activation of CREB was also depressed, and the malignant biological behaviors were weakened accordingly. The GOF-mutant SHP2 promoted GBM cell proliferation, metastasis, and tumor growth through the ERK/CREB pathway, providing a promising target for the treatment of GBM.
  • ||||||||||  quercetin (LY294002) / Eli Lilly, U0126 / Promega
    Journal:  Tanshinone IIA reverses EGF- and TGF-β1-mediated epithelial-mesenchymal transition in HepG2 cells via the PI3K/Akt/ERK signaling pathway. (Pubmed Central) -  Dec 8, 2019   
    Furthermore, western blot analysis confirmed that blocking the function of PI3K/Akt and ERK with LY294002 and U0126 resulted in upregulation of E-cadherin expression, and downregulation of vimentin and Snail expression in EGF- and TGF-β1-treated HepG2 cells. In conclusion, to the best of our knowledge, the results of the present study are the first to indicate that Tan IIA may suppress EGF- and TGF-β1-induced EMT in HepG2 cells by deactivating the PI3K/Akt/ERK pathway.
  • ||||||||||  Garamycin (gentamicin sulfate) / Generic Mfg.
    Journal:  STK33 alleviates gentamicin-induced ototoxicity in cochlear hair cells and House Ear Institute-Organ of Corti 1 cells. (Pubmed Central) -  Dec 6, 2019   
    Moreover, STK33 was involved in extracellular signal-regulated kinase 1/2 pathway in primary culture of HCs and HEI-OC1 cells in response to gentamicin insult. The findings from this work indicate that STK33 decreases the sensitivity to the apoptosis dependent on mitochondrial apoptotic pathway by regulating ROS generation after gentamicin treatment, which provides a new potential target for protection from the aminoglycoside-induced ototoxicity.
  • ||||||||||  PIK-75 / Pathway Therapeutics, U0126 / Promega, PD98059 / Wayne State University
    Journal:  Role of PI3K/Akt and MEK/ERK Signalling in cAMP/Epac-Mediated Endothelial Barrier Stabilisation. (Pubmed Central) -  Dec 5, 2019   
    Inhibition of MEK/ERK but not PI3K/Akt signalling enhances barrier stabilising and barrier protective effects of cAMP/Epac activation. 8-pCPT-2'-O-Me-cAMP (PubChem CID: 9913268); Akt inhibitor VIII (PubChem CID: 10196499); AS-252424 (PubChem CID: 11630874); IC-87114 (PubChem CID: 9908783); PD 98059 (PubChem CID: 4713); PIK-75 (PubChem CID: 10275789); TGX-221 (PubChem CID: 9907093); Thrombin (PubChem CID: 90470996); U0126 (PubChem CID: 3006531); Wortmannin (PubChem CID: 312145).
  • ||||||||||  U0126 / Promega
    Journal, IO Biomarker:  The C-terminus of the amelogenin peptide influences the proliferation of human bone marrow mesenchymal stem cells. (Pubmed Central) -  Nov 30, 2019   
    This study identified a common factor between inflammation and vascularization in OA as well as a new therapeutic target for OA: ERRγ. A C-terminal amelogenin variant increased the proliferation of MSCs via an interaction with LAMP1 and the MAPK-ERK signaling pathway, indicating the possibility of using MSCs for tissue regeneration in the craniofacial region.