- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega
Journal: Liquiritin and Liquiritigenin Induce Melanogenesis via Enhancement of p38 and PKA Signaling Pathways. (Pubmed Central) - Jun 27, 2019
Furthermore, LQ- or LQG-mediated melanin synthesis was partially blocked by p38 inhibitor (SB203580) and protein kinase A (PKA) inhibitor (H-89); however, ERK kinase (MEK) inhibitor (U0126) and phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002) had no effect. The results suggest that LQ and LQG enhance melanin synthesis by upregulating the expression of melanogenic enzymes, which were activated by p38 and PKA signaling pathways, leading to MITF expression and CREB phosphorylation.
- |||||||||| low molecular weight dextran sulfate (ILB) / TikoMed, U0126 / Promega
Journal: CTGF-mediated ERK signaling pathway influences the inflammatory factors and intestinal flora in ulcerative colitis. (Pubmed Central) - Jun 23, 2019
The results suggest that LQ and LQG enhance melanin synthesis by upregulating the expression of melanogenic enzymes, which were activated by p38 and PKA signaling pathways, leading to MITF expression and CREB phosphorylation. Inhibiting CTGF could improve inflammatory response and intestinal flora to partially reverse DSS-induced UC via blocking ERK signaling pathway.
- |||||||||| U0126 / Promega
Journal: ERK1/2 regulates heat stress-induced lactate production via enhancing the expression of HSP70 in immature boar Sertoli cells. (Pubmed Central) - Jun 17, 2019
...Pretreatment with U0126 (1 × 10 mol/L), a highly selective inhibitor of ERK1/2 phosphorylation, reduced HSP70, GLUT3, and LDHA expressions and decreased LDH activity and lactate production...These results show that activated ERK1/2 increases heat stress-induced lactate production by enhancing HSP70 expression to promote the expressions of molecules related to lactate production (GLUT3 and LDHA). Our study reveals a new insight in reducing the negative effect of heat stress in boars.
- |||||||||| U0126 / Promega, PD98059 / Wayne State University
Biomarker, Journal: CX3CL1 promotes MMP-3 production via the CX3CR1, c-Raf, MEK, ERK, and NF-κB signaling pathway in osteoarthritis synovial fibroblasts. (Pubmed Central) - Jun 15, 2019
Our study reveals a new insight in reducing the negative effect of heat stress in boars. Our results demonstrate that CX3CL1 activates c-Raf, MEK, ERK, and NF-κB on the MMP-3 promoter through CX3CR1, thus contributing to cartilage destruction during OA.
- |||||||||| U0126 / Promega
Journal: Downregulation of heat shock factor 4 transcription activity via MAPKinase phosphorylation at Serine 299. (Pubmed Central) - Jun 15, 2019
...Using the rabbit polyclonal antibody against phospho-S299 of HSF4, we found that EGF and ectopic expression of MEK1 can increase the phosphorylation of HSF4/S299 and induce HSF4 sumoylation, and these effects are inhibited by U0126...Interestingly, ERK1/2 activity is lower in P3 lens than in P7 and P14 lens, which is in line with the phosphorylation of HSF4/S299. Taken together, our data demonstrate that HSF4/299 is a phosphorylation target of MEK1-ERK1/2, and phosphorylation of S299 is responsible for tuning down HSF4 transcription activity during postnatal lens development.
- |||||||||| U0126 / Promega, SP600125 / Celgene
Journal: Anti-Wrinkling and Anti-Melanogenic Effect of Pradosia mutisii Methanol Extract. (Pubmed Central) - Jun 9, 2019
These findings suggested that inhibition of JNK and p38 and activation of ERK could be targeted by Pm-ME. Therefore, Pm-ME may exert anti-photoaging and anti-melanogenic properties via the regulation of mitogen-activated protein kinase, which could be beneficial in the cosmeceutical industry.
- |||||||||| U0126 / Promega
Journal: c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs. (Pubmed Central) - Jun 7, 2019
Administration of ERK inhibitor U0126 impeded the development of rectal prolapse in c-Abl deficient mice. These results reveal a role for c-Abl-regulated smooth muscle proliferation in the pathogenesis of rectal prolapse, and imply that long-term use of imatinib mesylate may cause gastrointestinal problems in patients while ERK inhibitor may be effective in treating rectal prolapse.
- |||||||||| U0126 / Promega, SP600125 / Celgene
Journal: ERK1/2 mediates the lipopolysaccharide-induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts. (Pubmed Central) - Jun 6, 2019
Inhibition assays on MAPKs using U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor) and QNZ (NFκB inhibitor) show that LPS-induced upregulation of FGF-2, uPA, MMP-2 and MMP-9 in cardiac fibroblasts was mediated through ERK1/2 signaling. Collectively, our results provide a link between LPS-induced cardiac dysfunction and ERK1/2 signaling pathway and thereby implies ERK1/2 as a possible target to regulate LPS induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts.
- |||||||||| U0126 / Promega
Preclinical, Journal: CTGF Contributes to the Development of Posterior Capsule Opacification: an in vitro and in vivo study. (Pubmed Central) - May 30, 2019
...MEK inhibitor U0126 effectively restrained the CTGF-induced expression of α-smooth muscle actin (α-SMA), fibronectin (Fn) and type I collagen (COL-1) in HLECs...In conclusion, CTGF contributed to the development of PCO presumably by promoting proliferation, migration of LECs, EMT specific protein expression and ECM synthesis in HLECs, which is dependent on ERK signalling. Furthermore, blocking CTGF effectively inhibited PCO in the rats and the EMT specific protein expression in the lens capsule.
- |||||||||| U0126 / Promega
Journal: Cascade Signals of Papaverine Inhibiting LPS-Induced Retinal Microglial Activation. (Pubmed Central) - May 30, 2019
...The cAMP inhibitor Rp-isomer, PKA inhibitor H89, and MEK inhibitor U0126 were separately added to further investigate the role of MEK/Erk in PAP inhibition of primary microglial activation and the relationship between cAMP/PKA and MEK/Erk...Both Rp-isomer and H89 upregulated the phosphorylation levels of MEK and Erk. Papaverine may inhibit inflammatory factors and promote the expression of anti-inflammatory factors through the cAMP/PKA and MEK/Erk pathway, thereby inhibiting LPS-induced activation of primary retinal microglia, and the MEK/Erk pathway may be partially regulated by cAMP/PKA, which can provide theoretical basis and experimental basis for its protection of the central nervous system.
- |||||||||| U0126 / Promega
Journal: MEK inhibition prevents TGF‑β1‑induced myofibroblast transdifferentiation in human tenon fibroblasts. (Pubmed Central) - May 29, 2019
Mechanistically, U0126 suppressed the TGF‑β1‑stimulated phosphorylation of mothers against decapentaplegic homolog 2/3, P38 mitogen‑activated protein kinase and extracellular signal‑regulated kinase 1/2, indicating that U0126 may inhibit HTF activation through the canonical and non‑canonical signaling pathways of TGF‑β1. Therefore, U0126 exhibits a potent anti‑fibrotic effect among HTFs, and the inhibition of MEK signaling may serve as an alternative intervention strategy for the treatment of trabeculectomy‑associated fibrosis.
- |||||||||| selumetinib (AZD6244) / Merck (MSD), AstraZeneca, U0126 / Promega
Preclinical, Journal: Efficacy of MEK inhibition in a K-Ras-driven cholangiocarcinoma preclinical model. (Pubmed Central) - May 24, 2019
Altogether, our study demonstrates that K-Ras/NICD mice represent a novel and useful preclinical model to study K-Ras-driven iCCA development and the effectiveness of MEK inhibitors in counteracting this process. Our data support the usefulness of MEK inhibitors for the treatment of human iCCA.
- |||||||||| U0126 / Promega
Preclinical, Journal: Drp1 phosphorylation by MAPK1 causes mitochondrial dysfunction in cell culture model of Huntington's disease. (Pubmed Central) - May 18, 2019
...Drp1 phosphorylation at serine 616 is increased in HD knock-in mouse derived striatal cells, which is abolished by treatment with U0126, a potent inhibitor of MEK1/2...This study suggests that in HD, MAPK1 activation leads to the aberrant mitochondrial fission and mitochondrial function by phosphorylating Drp1. Therefore, inhibition of Drp1-mediated excessive mitochondrial fission might be a strategy for development of therapy for treating HD.
- |||||||||| U0126 / Promega
Journal: SIRT2, ERK and Nrf2 Mediate NAD Treatment-Induced Increase in the Antioxidant Capacity of PC12 Cells Under Basal Conditions. (Pubmed Central) - May 14, 2019
...The NAD-induced changes can also be blocked by the ERK signaling inhibitor U0126...Collectively, our study has provided the first evidence that NAD can enhance directly the antioxidant capacity of the cells under basal conditions, which is mediated by SIRT2, ERK, and Nrf2. These findings have suggested not only the great nutritional potential of NAD, but also a novel mechanism underlying the protective effects of the NAD administration in the disease models: the NAD administration can enhance the resistance of the normal cells to oxidative insults by increasing the antioxidant capacity of the cells.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega
Biomarker, Journal: CXC chemokine receptor 4 regulates breast cancer cell cycle through S phase kinase associated protein 2 (Pubmed Central) - May 13, 2019
These findings have suggested not only the great nutritional potential of NAD, but also a novel mechanism underlying the protective effects of the NAD administration in the disease models: the NAD administration can enhance the resistance of the normal cells to oxidative insults by increasing the antioxidant capacity of the cells. CXCR4 can affect cell cycle and inhibit the proliferation of breast cancer cells by regulating Skp2 gene expression through PI3K/Akt and ERK signaling pathway.
- |||||||||| daporinad (APO866) / Onxeo
Journal: Effects of FK866 on migration of A549 cells and related mechanism (Pubmed Central) - May 11, 2019
s: Low concentration of FK866 decreases the migration of A549 cells through the inhibition of NAD level, activation of ERK1/2 and up-regulation of E-cadherin expression. However, it also up-regulates the expression of vimentin, indicating that it may have dual effects on the migration of tumor cells.
- |||||||||| U0126 / Promega
Journal: Effect of lower chlorinated hydroxylated-polychlorobiphenyls on development of PC12 cells. (Pubmed Central) - May 8, 2019
Moreover, these neuronal elongations were suppressed by U0126, and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was observed in PC12 cells treated with 4OH-PCB2, 4'OH-PCB25, and 4'OH-PCB159. Taken together, our results indicate that the effect of OH-PCB on neuronal development is not dependent on the number of chlorine groups but on the chemical structure, and the mitogen-activated kinase kinase (MEK)-ERK1/2 signaling pathway is involved in this process.
- |||||||||| U0126 / Promega
Journal: Extracellular ADP facilitates monocyte recruitment in bacterial infection via ERK signaling. (Pubmed Central) - May 7, 2019
Accordingly, ADP-induced MCP-1 production and protection against bacterial infection could also be reduced by U0126, forskolin and 8-bromo-cAMP. Overall, our study reveals a relationship between danger signals and innate immune responses, which suggests the potential therapeutic significance of ADP-mediated purinergic signaling in infectious diseases.Cellular & Molecular Immunology advance online publication, 21 November 2016; doi:10.1038/cmi.2016.56.
- |||||||||| 7-Hydroxystaurosporine (UCN-01) / National Cancer Institute
Preclinical, Journal: The combination of UCN-01 and ATRA triggers differentiation in ATRA resistant acute promyelocytic leukemia cell lines via RAF-1 independent activation of MEK/ERK. (Pubmed Central) - May 7, 2019
With the introduction of arsenic trioxide and all-trans retinoic acid, the prognosis of acute promyelocytic leukemia has greatly improved...U0126 (MEK specific inhibitor) not only suppressed the combination-induced differentiation but also restored the protein level of CCAAT/enhancer binding protein β and/or PU.1...Therefore, the combination overcame differentiation block via RAF-1 independent MEK/ERK modulation of the protein level of CCAAT/enhancer binding protein β and/or PU.1. These findings may provide a preclinical rationale for the potential role of this combination in the treatment of all-trans retinoic acid resistant acute promyelocytic leukemia patients.
- |||||||||| dexamethasone / generics
Journal: Geniposide Alleviates Glucocorticoid-Induced Inhibition of Osteogenic Differentiation in MC3T3-E1 Cells by ERK Pathway. (Pubmed Central) - May 7, 2019
...In this study, we investigated the protective effects of geniposide on dexamethasone (DEX)-induced osteogenic inhibition in MC3T3-E1 cells...The ERK activation inhibitor U0126 and glucagon-like peptide-1 (GLP-1) receptor antagonist exendin 9-39 abolished the geniposide-induced activation of ERK and inhibited the protective effect of geniposide...The effect of geniposide was at least partially associated with activating ERK signaling pathway via GLP-1 receptor. Geniposide might be a potential therapeutic agent for GC-induced osteoporosis.
- |||||||||| U0126 / Promega, PD98059 / Wayne State University
Journal: AKR1B10 Activates Diacylglycerol (DAG) Second Messenger in Breast Cancer Cells. (Pubmed Central) - May 7, 2019
In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two-dimension (2D) and three-dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway.
- |||||||||| dexamethasone / generics, sirolimus / generics
Journal: The vaccine adjuvant MPLA activates glycolytic metabolism in mouse mDC by a JNK-dependent activation of mTOR-signaling. (Pubmed Central) - May 1, 2019
The MPLA-induced activation of glycolytic metabolism in mouse mDC was shown to depend on a JNK-mediated activation of mTOR-signaling, while both MAPK- and NFB-signaling contributed to pro-inflammatory cytokine secretion. Understanding the mechanisms by which MPLA activates dendritic cells will both improve our understanding of its adjuvant properties and contribute to the future development and safe application of this promising adjuvant.
- |||||||||| U0126 / Promega, SP600125 / Celgene
Journal: HMGB1-induced angiogenesis in perforated disc cells of human temporomandibular joint. (Pubmed Central) - May 1, 2019
Tube formation of human umbilical vein endothelial cells (HUVECs) was significantly increased by exposure to conditioned medium derived from HMGB1-stimulated perforated disc cells, while attenuated with pre-treatment of inhibitors for VEGF, HIF-1α, Erk and JNK, individually. Therefore, abundance of HMGB1 mediates activation of HIF-1α in disc cells via Erk and JNK pathway and then, initiates VEGF secretion, thereby leading to disc angiogenesis and accelerating degenerative change of the perforated disc.
- |||||||||| U0126 / Promega
Journal: A feedback regulation of CREB activation through the CUL4A and ERK signaling. (Pubmed Central) - Apr 28, 2019
...Moreover, the inhibition of ERK pathway by U0126 not only reduces the CREB activation but also the CUL4A levels suggesting that CREB is the upstream activator of CUL4A transcription...It is reported that CUL4A activates the ERK1/2 transcription and ERK1/2 pathway activates the CREB by phosphorylation. Based on our data and earlier findings, we report that CREB regulates the CUL4A levels positively which in turn activates the CREB through ERK1/2 pathway in the form of auto-regulatory looped mechanism.This suggests that CUL4A might be involved in proliferation of cancer cells by regulating the ERK1/2 and CREB signaling.
- |||||||||| U0126 / Promega
Journal: Sex Differences in the Rapid Cell Signaling Mechanisms Underlying the Memory-Enhancing Effects of 17β-Estradiol. (Pubmed Central) - Apr 20, 2019
E increased phospho-CREB levels in both sexes, yet U0126 did not block these increases in castrated or intact males, indicating that E regulates CREB phosphorylation in males via an ERK-independent mechanism. Collectively, these findings suggest that the beneficial effects of hippocampal E on memory consolidation in males and females are mediated by different molecular mechanisms, which has important implications for the development of treatments to reduce memory dysfunction in men and women.
- |||||||||| Preclinical, Journal: NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A:Allergen Fusion Protein. (Pubmed Central) - Apr 18, 2019
...The influence of mammalian target of rapamycin (mTOR)-, NF?B-, and MAP kinase (MAPK)-signaling on cytokine secretion and metabolic activity of bone marrow (BM)-derived mDCs stimulated with rFlaA:Betv1 were investigated by pre-treatment with either mTOR- (rapamycin), NF?B- (dexamethason, BMS-345541, TPCA-1, triptolide, or BAY-11) or MAPK- (SP600125, U0126, or SB202190) inhibitors, respectively...Notably, with the exception of a partial JNK-dependency, rFlaA:Betv1-mediated effects on mDC metabolism were mostly NF?B- and MAPK-independent. Therefore, MAPK-mediated activation of both NFκB- and mTOR-signaling likely is a key pathway for the production of pro- and anti-inflammatory cytokines by flagellin fusion protein vaccines.
- |||||||||| Xeljanz (tofacitinib) / Pfizer
Journal: JAK3 and PI3K mediates bovine Interferon-tau stimulated gene expression in the blood neutrophils. (Pubmed Central) - Apr 17, 2019
Similarly, western blot analysis of neutrophil protein fraction showed weak signals of ISG15, OAS1, pJAK3 and PI3K in the presence of pJAK3 and PI3K inhibitors. The expression profile, immunocytochemistry and western blot analysis revealed a JAK3 and PI3K mediated Interferon-tau stimulated gene expression in blood neutrophils.
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