U0126 / Promega 
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  • ||||||||||  U0126 / Promega, Zelboraf (vemurafenib) / Roche
    Journal:  Long glucocorticoid-induced leucine zipper regulates human thyroid cancer cell proliferation. (Pubmed Central) -  Nov 28, 2019   
    Treatment with MAPK inhibitors led to the phosphorylation of the cAMP/response element-binding protein (CREB), and active CREB bound to the L-GILZ promoter, contributing to its transcription. We suggest that the CREB signaling pathway, frequently deregulated in thyroid tumors, is involved in L-GILZ upregulation and that L-GILZ regulates thyroid cancer cell proliferation, which may have potential in cancer treatment.
  • ||||||||||  U0126 / Promega
    Preclinical, Journal:  Microcystin-LR influences the in vitro oocyte maturation of zebrafish by activating the MAPK pathway. (Pubmed Central) -  Nov 18, 2019   
    Moreover, the MAPK inhibitors (10 μM) were applied to explore the role of MAPK subtypes during MC-LR influencing OM and results showed that ERK inhibitor U0126 and p38 inhibitor SB203580 mitigated the effects of 100 μg/L MC-LR-induced MAPK hyper-phosphorylation and elevated GVBD in the oocytes. In conclusion, the present study indicates that microcystins disrupt the meiotic maturation by the pathway of MC-PP2A-MAPK-OM due to the phosphorylation disorder in oocytes.
  • ||||||||||  quercetin (LY294002) / Eli Lilly, Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo, U0126 / Promega
    Journal:  Nitric oxide: Is it the culprit for the continued expansion of keloids? (Pubmed Central) -  Nov 14, 2019   
    In this study, we investigated the effect of NO on KDFs proliferation by Sodium Nitroprusside (SNP), an NO donor...U0126 and LY294002, inhibitors of Erk and Akt respectively, block SNP-enhanced KDFs proliferation effectively...Moreover, it decreased the expression of p, a cell cycle inhibitor. Our results reveal that SNP induced KDFs proliferation and loss contact inhibition led to pile up growth via activation of the Erk and Akt pathways, as well as a decreased expression of p. Thus, we speculate that the pathological feature of continuous expansion in keloids is caused by NO-induced KDFs sustained growth.
  • ||||||||||  U0126 / Promega
    Journal:  TGF-β1 facilitates cell-cell communication in osteocytes via connexin43- and pannexin1-dependent gap junctions. (Pubmed Central) -  Nov 1, 2019   
    TGF-β1 increased the accumulation of Smad3 in the nuclear region (immunofluorescence assay) and promoted the enrichment of Smad3 at the binding sites of the promoters of Gja1 (Cx43) and Panx1 (ChIP assay), thereby initiating the enhanced gene expression. These results provide a deep understanding of the molecular mechanisms involved in the modulation of cell-cell communication in osteocytes induced by TGF-β1.
  • ||||||||||  low molecular weight dextran sulfate (ILB) / TikoMed, U0126 / Promega, SP600125 / Celgene
    Preclinical, Journal, IO Biomarker:  IgG plasma cells initiate changes in the protein C system in mouse ulcerative colitis through CD14+CD64+ macrophage activation. (Pubmed Central) -  Oct 31, 2019   
    There is a possibility that the interaction between IgG plasma cells and CD14+CD64+ macrophages, as well as further secretion of cytokines from CD14+CD64+ macrophages by the formation and stimulation of IgG-IC, subsequently influence MVECs through the β-arrestin-MAPK pathway. Enhancement of PCS activity may represent a novel approach for treating UC.
  • ||||||||||  U0126 / Promega
    Preclinical, Journal:  Potent block of potassium channels by MEK inhibitor U0126 in primary cultures and brain slices. (Pubmed Central) -  Oct 16, 2019   
    Despite the potent and reversible action of U0126 on K channels, PD98059, a structurally-unrelated MEK inhibitor, did not induce such an effect, suggesting U0126 may act independently of MEK inhibition. Together, these results raise cautions for using U0126 as a specific inhibitor for studying MEK signaling in neurons; on the other hand, further studies on the blocking mechanisms of U0126 as a potent inhibitor of K may provide useful insights into the structure-function relationship of K in general.
  • ||||||||||  U0126 / Promega
    Knockdown of Central (Pro)Renin Receptor Attenuates Renal Injury in a High-Salt-Load CKD Rat Model (Exhibit Hall, Walter E. Washington Convention Center) -  Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3782;    
    Protocol B, U0126, Wortmannin and Losartan were used to inhibit MAPK/ERK1/2,PI3K/Akt signaling pathway, and ACE1-Ang II-AT1 axis in CKD model by continuous central administration and a high-salt diet was given for 4 weeks, respectively...Central PRR may affect renal pathology through the ACE1-Ang II-AT1 axis as well as MAPK/ERK1/2 and PI3K/Akt signaling pathways. Funding Government Support - Non-U.S.
  • ||||||||||  Alverix (amiloride hydrochloride) / Remedica, U0126 / Promega
    Chronic Fluid Shear Stress (FSS) Induces ERK Dependent Sodium Transport in Principal Cells (PCs) (Exhibit Hall, Walter E. Washington Convention Center) -  Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2849;    
    Methods To test this, murine PCs (mpkccd) were grown on snapwells under static conditions or exposed to 0.4 dynes/cm2 of FSS for 24 hrs and amiloride sensitive Na current (Iasc) measured in an Ussing chamber...Next, we tested whether U0126, a MEK inhibitor, could recover the FSS mediated reduction in Iasc...In sham kidneys pERK co-localized with PC cells; however, in nephrectomized mice pERK chiefly co-localized with DBA and in a minority of cells localized with non-DBA stained cells of the CCD. Conclusion Chronic FSS induces ERK to stimulate ENaC dependent Na transport in vitro, and in vivo pERK is expressed primarily in PCs, suggesting ERK may play an identical role in vivo Funding Veterans Affairs Support
  • ||||||||||  Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
    Identification of a Novel Smad Target in SGLT2-Mediated CTGF/CCN2 Expression (Exhibit Hall, Walter E. Washington Convention Center) -  Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2705;    
    Hayashida (2013) showed that glucose mediated ERK activation of LR potentiated Smad regulated transcription in mesangial cells. As MEK inhibition was able to reverse LR phosphorylation in our PTECs, our data indicates an important role for ERK in facilitating the observed glucose mediated pro-fibrotic effect.
  • ||||||||||  U0126 / Promega
    Preclinical, Journal, IO Biomarker:  Interleukin-1β Induces Apoptosis in Annulus Fibrosus Cells through the Extracellular Signal-regulated Kinase Pathway. (Pubmed Central) -  Oct 13, 2019   
    Three experimental groups were established, including Control, IL-1β, and IL-1β+U0126 groups, respectively...Furthermore, apoptosis-related gene expression levels of B-cell lymphoma-2 associated X (Bax), caspase-3, and caspase-9 were decreased significantly compared with the IL-1β group, and the expression level of B-cell lymphoma-2 (Bcl-2) was increased significantly compared with the IL-1β group. These results suggest that IL-1β induces apoptosis in AFCs through the ERK pathway, and ERK inhibition may provide some protection against the adverse effects of IL-1β.
  • ||||||||||  sirolimus / generics
    Journal:  Ecdysteroidogenesis and development in Heliothis virescens (Lepidoptera: Noctuidae): focus on PTTH-stimulated pathways. (Pubmed Central) -  Sep 28, 2019   
    In larvae fed on diet supplemented with rapamycin, the growth of PGs was suppressed, and ecdysone production and secretion were inhibited. Overall, the in vivo and in vitro results demonstrated that, similarly to Bombyx mori, MAPK and PI3K/Akt/TOR pathways are involved in PTTH signaling-stimulated ecdysteroidogenesis, and indicated the important role of TOR protein in H. virescens systemic growth.
  • ||||||||||  U0126 / Promega
    Journal:  SCF promotes the production of IL-13 via the MEK-ERK-CREB signaling pathway in mast cells. (Pubmed Central) -  Sep 27, 2019   
    However, JSI-124 (JAK/STAT3 pathway inhibitor), Wortmannin (PI3K/Akt pathway inhibitor) and PDTC (NF-κB inhibitor) had no effect on the role of SCF promoting the P815 cells producing IL-13. Therefore, SCF signaling promotes mast cell P815 to produce IL-13, and this effect is associated with the MEK-ERK-CREB signaling pathway.
  • ||||||||||  U0126 / Promega
    Journal, IO Biomarker:  Phosphorylation of TMEM55B by Erk/MAPK regulates lysosomal positioning. (Pubmed Central) -  Sep 19, 2019   
    Of these stimuli, Toll-like receptor ligands most strongly induce TMEM55B phosphorylation, and this is blocked by the MEK1/2 inhibitor U0126...Overexpression of TMEM55B but not TMEM55A notably enhances lamp1 clustering, with TMEM55B mutants (lacking phosphorylation sites or mimicking the phosphorylated state) exhibiting lower and higher efficacies (respectively) than wild-type TMEM55B. Collectively, results suggest that phosphorylation of TMEM55B by Erk/MAPK impacts lysosomal dynamics.
  • ||||||||||  Myrbetriq (mirabegron) / Astellas
    Preclinical, Journal:  Effect of mirabegron on tight junction molecules in primary cultured rat Sertoli cells. (Pubmed Central) -  Sep 14, 2019   
    These results suggest that mirabegron treatment is associated with assembly of the blood-testis barrier through p44/42 MAPK pathway. These findings could explain one of the underlying mechanisms of reproductive toxicity induced by mirabegron.