PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34127699-8 2021 In conclusion, our study showed that selumetinib inhibited acrolein-activated Nrf-2-HO-1 pathway, acrolein-induced protein conjugation and aggregation as well as damage in neurite outgrowth and cell death, suggesting that selumetinib, a MEK-ERK inhibitor, may be a potential neuroprotective agent against acrolein-induced neurotoxicity in the CNS neurodegenerative diseases. AZD 6244 37-48 mitogen-activated protein kinase 1 Homo sapiens 241-244 34127699-8 2021 In conclusion, our study showed that selumetinib inhibited acrolein-activated Nrf-2-HO-1 pathway, acrolein-induced protein conjugation and aggregation as well as damage in neurite outgrowth and cell death, suggesting that selumetinib, a MEK-ERK inhibitor, may be a potential neuroprotective agent against acrolein-induced neurotoxicity in the CNS neurodegenerative diseases. AZD 6244 222-233 mitogen-activated protein kinase 1 Homo sapiens 241-244 34127699-2 2021 In the present study, the neuroprotective effect of selumetinib (a MEK-ERK inhibitor) on acrolein-induced neurotoxicity was investigated in vitro using primary cultured cortical neurons. AZD 6244 52-63 mitogen-activated protein kinase 1 Homo sapiens 71-74 34127699-4 2021 Co-treatment of selumetinib blocked acrolein-induced ERK phosphorylation. AZD 6244 16-27 mitogen-activated protein kinase 1 Homo sapiens 53-56 33978635-10 2021 Conclusions: Selumetinib reduces MAPK signaling in tissues clinically relevant to NF1, effectively normalizing p-ERK to WT levels in optic nerve but resulting in abnormally low levels of p-ERK in the skin. AZD 6244 13-24 mitogen-activated protein kinase 1 Homo sapiens 113-116 33405090-2 2021 We conducted a biomarker-driven trial of selumetinib (KOSELUGO ; ARRY-142886), an orally active, allosteric mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, in pancreas cancer patients with somatic KRASG12R mutations. AZD 6244 41-52 mitogen-activated protein kinase 1 Homo sapiens 108-148 33978635-8 2021 Basal p-ERK levels were significantly higher in NF1 minipig optic nerve compared to WT and were reduced to WT levels (60%) with selumetinib. AZD 6244 128-139 mitogen-activated protein kinase 1 Homo sapiens 8-11 35289492-3 2022 Selumetinib is an oral selective inhibitor of RAS-mitogen-activated protein kinase (MAPK) 1 and 2, which has shown efficacy for tumour shrinkage/stabilisation and symptom improvement. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 46-97 33978635-10 2021 Conclusions: Selumetinib reduces MAPK signaling in tissues clinically relevant to NF1, effectively normalizing p-ERK to WT levels in optic nerve but resulting in abnormally low levels of p-ERK in the skin. AZD 6244 13-24 mitogen-activated protein kinase 1 Homo sapiens 189-192 31942645-6 2020 In this study, we demonstrate that the MEK/ERK inhibitor AZD6244 has potent antiviral efficacy in vitro against DENV-2, DENV-3, and Saint Louis encephalitis virus (SLEV). AZD 6244 57-64 mitogen-activated protein kinase 1 Homo sapiens 43-46 32533336-3 2020 Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, was reported to induce a clinical response in pediatric subjects with inoperable PN. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 29-75 32629964-8 2020 The combination of MLN3651 and the MEK1/2 inhibitor selumetinib prevented the increase in Raf/MEK/ERK activity, and had an additive effect compared with either treatment alone. AZD 6244 52-63 mitogen-activated protein kinase 1 Homo sapiens 98-101 32181767-9 2020 Finally, in non-V600 BRAF mutant cell lines combined inhibition of pan-RAF and MEK with sorafenib/AZ628 and selumetinib showed significantly stronger cell growth, cell migration and Erk activation inhibition and also increased apoptosis induction compared to single treatments. AZD 6244 108-119 mitogen-activated protein kinase 1 Homo sapiens 182-185 33549085-4 2021 Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, has been the first molecule to demonstrate the ability of tackling the growth of PNs. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 29-75 32504375-1 2020 Selumetinib (KOSELUGOTM; AZD6244, ARRY-142886) is a mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor being developed by AstraZeneca for the treatment of tumours associated with neurofibromatosis and various cancers. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 52-92 32504375-1 2020 Selumetinib (KOSELUGOTM; AZD6244, ARRY-142886) is a mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor being developed by AstraZeneca for the treatment of tumours associated with neurofibromatosis and various cancers. AZD 6244 25-32 mitogen-activated protein kinase 1 Homo sapiens 52-92 32504375-1 2020 Selumetinib (KOSELUGOTM; AZD6244, ARRY-142886) is a mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor being developed by AstraZeneca for the treatment of tumours associated with neurofibromatosis and various cancers. AZD 6244 34-45 mitogen-activated protein kinase 1 Homo sapiens 52-92 31201369-10 2019 Based on the HPC3 cell model, we found that the DSTYK mutation promoted cell migration and invasion of HPC3 cells via activation of ERK1/2 signaling, which was inhibited by the MEK/ERK inhibitor AZD6244. AZD 6244 195-202 mitogen-activated protein kinase 1 Homo sapiens 132-135 31285371-6 2019 Moreover, a novel TGFbeta1/ERK/PHD2-mediated pathway regulating HIF1alpha stability in PROC was discovered.Results: YC-1 and selumetinib resensitized PROC cells to cisplatin. AZD 6244 125-136 mitogen-activated protein kinase 1 Homo sapiens 27-30 31285371-10 2019 Inhibition of TGFbeta1 by SB431542, ERK by selumetinib, or HIF1alpha by YC-1 efficiently overcame platinum resistance both in vitro and in vivo The results from clinical samples confirm activation of the ERK/PHD2/HIF1alpha axis in patients with PROC, correlating highly with poor prognoses for patients.Conclusions: HIF1alpha stabilization is regulated by TGFbeta1/ERK/PHD2 axis in PROC. AZD 6244 43-54 mitogen-activated protein kinase 1 Homo sapiens 36-39 30317534-1 2019 Introduction Selumetinib (AZD6244, ARRY-142886) is a potent inhibitor of MEK1/2, thereby inhibiting phosphorylation of ERK2. AZD 6244 13-24 mitogen-activated protein kinase 1 Homo sapiens 119-123 30317534-1 2019 Introduction Selumetinib (AZD6244, ARRY-142886) is a potent inhibitor of MEK1/2, thereby inhibiting phosphorylation of ERK2. AZD 6244 26-33 mitogen-activated protein kinase 1 Homo sapiens 119-123 30317534-1 2019 Introduction Selumetinib (AZD6244, ARRY-142886) is a potent inhibitor of MEK1/2, thereby inhibiting phosphorylation of ERK2. AZD 6244 35-46 mitogen-activated protein kinase 1 Homo sapiens 119-123 30343534-3 2018 Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. AZD 6244 79-90 mitogen-activated protein kinase 1 Homo sapiens 138-141 30706361-5 2019 HCT116 cell resistance to MEK inhibitor AZD6244, which inhibited the activation of ERK and promoted the activation of JAK2-STAT3 signaling. AZD 6244 40-47 mitogen-activated protein kinase 1 Homo sapiens 83-86 30706361-6 2019 The combination treatment of AZD6244 and AG490 significantly inhibited cell viability and induced cell apoptosis, and completely inhibited the activation of ERK and JAK2-STAT3 signaling. AZD 6244 29-36 mitogen-activated protein kinase 1 Homo sapiens 157-160 30579838-7 2019 Induction of thymidine kinase 1, a rate-limiting enzyme in salvage pathway, by 5-FU was abrogated by subsequent treatment with selumetinib, and ERK reactivation after selumetinib was prohibited by pretreatment with 5-FU. AZD 6244 167-178 mitogen-activated protein kinase 1 Homo sapiens 144-147 30771306-9 2019 Restored inhibition of MAPK signaling by selumetinib led to an increase in autophagic flux in vivo. AZD 6244 41-52 mitogen-activated protein kinase 1 Homo sapiens 23-27 31040916-6 2019 Treatment with a combination of SAB298 and AZD6244 (selumetinib), induced a synergistic growth inhibition, suggesting that the new compound could be used in the clinic as a substitute for, or in combination with MAPK inhibitors. AZD 6244 43-50 mitogen-activated protein kinase 1 Homo sapiens 212-216 31040916-6 2019 Treatment with a combination of SAB298 and AZD6244 (selumetinib), induced a synergistic growth inhibition, suggesting that the new compound could be used in the clinic as a substitute for, or in combination with MAPK inhibitors. AZD 6244 52-63 mitogen-activated protein kinase 1 Homo sapiens 212-216 30343534-5 2018 Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 34-38 30343534-5 2018 Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 65-68 30343534-6 2018 Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. AZD 6244 102-113 mitogen-activated protein kinase 1 Homo sapiens 15-18 30343534-11 2018 ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor. AZD 6244 109-120 mitogen-activated protein kinase 1 Homo sapiens 0-3 27713506-10 2016 Therefore, we suggest that clinical use of a combination of the MEK/ERK inhibitor AZD6244 and cisplatin might improve sensitivity to cisplatin-based chemotherapy and outcomes in NSCLC patients who harbor high-PAK1-expressing tumors. AZD 6244 82-89 mitogen-activated protein kinase 1 Homo sapiens 68-71 29719377-8 2018 Activation of ERK was inhibited by the pharmacological inhibitor selumetinib (AZD6244), which effectively promoted RAD001-induced cell death. AZD 6244 65-76 mitogen-activated protein kinase 1 Homo sapiens 14-17 29719377-8 2018 Activation of ERK was inhibited by the pharmacological inhibitor selumetinib (AZD6244), which effectively promoted RAD001-induced cell death. AZD 6244 78-85 mitogen-activated protein kinase 1 Homo sapiens 14-17 29670612-11 2018 C37, a small molecule blocking the interaction between FPRs and uPAR, and selumetinib, a clinically approved MAPKK/ERK inhibitor, significantly inhibited FPRs-mediated ROS production in fibroblasts derived from SSc patients. AZD 6244 74-85 mitogen-activated protein kinase 1 Homo sapiens 115-118 30172884-6 2018 Moreover, the upregulation of PD-L1 by chemotherapy was also attenuated by the treatment with erlotinib and a MAPK/MEK inhibitor (AZD6244), suggesting that PD-L1 is regulated by the EGFR/ERK pathway in ESCC. AZD 6244 130-137 mitogen-activated protein kinase 1 Homo sapiens 110-114 30172884-6 2018 Moreover, the upregulation of PD-L1 by chemotherapy was also attenuated by the treatment with erlotinib and a MAPK/MEK inhibitor (AZD6244), suggesting that PD-L1 is regulated by the EGFR/ERK pathway in ESCC. AZD 6244 130-137 mitogen-activated protein kinase 1 Homo sapiens 187-190 28791489-7 2017 RESULTS: Inhibition of ERK activation with selumetinib, a MEK1/2 inhibitor, blocked EGF-induced expansion of CD44+/CD24- populations. AZD 6244 43-54 mitogen-activated protein kinase 1 Homo sapiens 23-26 28424891-2 2017 Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 139-142 28424891-2 2017 Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. AZD 6244 13-20 mitogen-activated protein kinase 1 Homo sapiens 139-142 28424891-2 2017 Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. AZD 6244 22-33 mitogen-activated protein kinase 1 Homo sapiens 139-142 28620782-7 2017 Furthermore, when treating the triple mutant astrocytes with AZD-6244, an inhibitor of the RAF/MEK/ERK pathway, we found significant reduction in migration through the confined channels when compared to that of controls (83% decrease in 5 x 5 mum2 and 86% in 3 x 5 mum2 channels). AZD 6244 61-69 mitogen-activated protein kinase 1 Homo sapiens 99-102 27422710-5 2016 Selumetinib increased phosphorylation of KSR-1, a scaffolding protein required for assembly of MAPK signaling complex, as well as altered phosphorylation of GEF-H1, a novel regulator of KSR-1 and implicated in RAS-driven MAPK activation. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 95-99 27438013-0 2016 Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 95-98 27438013-3 2016 In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. AZD 6244 39-50 mitogen-activated protein kinase 1 Homo sapiens 78-81 27438013-4 2016 METHODS AND RESULTS: In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. AZD 6244 77-88 mitogen-activated protein kinase 1 Homo sapiens 117-120 27438013-5 2016 In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. AZD 6244 78-89 mitogen-activated protein kinase 1 Homo sapiens 111-114 27438013-8 2016 CONCLUSIONS: Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. AZD 6244 13-24 mitogen-activated protein kinase 1 Homo sapiens 134-137 26567773-1 2015 AZD6244 (ARRY-142886), a highly selective MAPK-ERK kinase inhibitor, has shown excellent clinical efficacy in many tumors. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 47-50 26802155-2 2016 Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 96-99 26802155-2 2016 Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway. AZD 6244 13-20 mitogen-activated protein kinase 1 Homo sapiens 96-99 26802155-2 2016 Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway. AZD 6244 22-33 mitogen-activated protein kinase 1 Homo sapiens 96-99 26384399-8 2015 We tested the hypothesis that targeted inhibition of the MAPK pathway by selumetinib inhibits acquisition of the breast cancer stem cell phenotype and prevents lung metastasis of TNBC. AZD 6244 73-84 mitogen-activated protein kinase 1 Homo sapiens 57-61 26567773-1 2015 AZD6244 (ARRY-142886), a highly selective MAPK-ERK kinase inhibitor, has shown excellent clinical efficacy in many tumors. AZD 6244 9-20 mitogen-activated protein kinase 1 Homo sapiens 47-50 26567773-11 2015 The anti-angiogenesis effect afford by AZD6244 may attribute to its modulation on p-ERK - c-Fos - HIF-1alpha - VEGF integrated signal pathways. AZD 6244 39-46 mitogen-activated protein kinase 1 Homo sapiens 84-87 24938872-6 2014 Collectively, our data indicate that miR-203 mediates the AZD6244-induced cytotoxicity of breast cancer cells and that the MEK/ERK/miR-203/CUL1 signaling pathway may participate in this process. AZD 6244 58-65 mitogen-activated protein kinase 1 Homo sapiens 127-130 26250606-9 2015 GSK2126458 decreased phospho-AKT while increasing phospho-ERK and AZD6244 decreased phospho-ERK efficiently while increasing phospho-AKT. AZD 6244 66-73 mitogen-activated protein kinase 1 Homo sapiens 92-95 26250606-10 2015 The combination of GSK2126458 and AZD6244 decreased both phospho-AKT and phospho-ERK effectively in vitro and in vivo. AZD 6244 34-41 mitogen-activated protein kinase 1 Homo sapiens 81-84 26250606-14 2015 CONCLUSIONS: The combination of GSK2126458 and AZD6244 blocks both the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways simultaneously and is an effective strategy for the treatment of CRPCs. AZD 6244 47-54 mitogen-activated protein kinase 1 Homo sapiens 83-86 25933683-11 2015 NVP-BEZ235 and AZD6244 reduced cell viability and induced cell cycle arrest and apoptosis, by reduction of p-AKT, p-S6, and p-ERK levels. AZD 6244 15-22 mitogen-activated protein kinase 1 Homo sapiens 126-129 25199829-6 2014 MEK inhibition induces RAS activation and BRAF-RAF1 dimerization and sustains MEK-ERK signaling, which is responsible for intrinsic resistance to selumetinib. AZD 6244 146-157 mitogen-activated protein kinase 1 Homo sapiens 82-85 25498501-0 2015 The glucosylceramide synthase inhibitor PDMP sensitizes pancreatic cancer cells to MEK/ERK inhibitor AZD-6244. AZD 6244 101-109 mitogen-activated protein kinase 1 Homo sapiens 87-90 25498501-1 2015 Here we show that d,l-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a glycosphingolipid biosynthesis inhibitor, increases the sensitivity of pancreatic cancer cells to the novel MEK-ERK inhibitor AZD-6244. AZD 6244 213-221 mitogen-activated protein kinase 1 Homo sapiens 199-202 25130256-2 2014 Here, we show that treatment of NRAS-mutant melanoma cell lines with the MEK inhibitors AZD6244 or trametinib resulted in a rebound activation of phospho-ERK (pERK). AZD 6244 88-95 mitogen-activated protein kinase 1 Homo sapiens 154-157 22310287-10 2013 Moreover, the combination of saracatinib and selumetinib effectively suppressed the growth and invasion of melanoma cells in a 3D environment, suggesting that combined inhibition of MEK and SRC is a promising approach to improve the efficacy of targeting the ERK/MAP kinase pathway in melanoma. AZD 6244 45-56 mitogen-activated protein kinase 1 Homo sapiens 259-262 23602735-7 2013 AZD6244 abrogated p-ERK and GDC0941 abrogated p-AKT levels, confirming their expected target effects. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 20-23 23602735-11 2013 CONCLUSION: Concomitant suppression of MEK/ERK and PI3K/AKT pathways by AZD6244 and GDC0941 abrogates compensatory mechanisms of tumor survival and causes synergistic cytotoxicity in thyroid cancer cells. AZD 6244 72-79 mitogen-activated protein kinase 1 Homo sapiens 43-46 23414467-4 2013 Importantly, as a MEK inhibitor, selumetinib could be particularly effective in tumors with a hyperactivated Ras/Raf/MEK/ERK pathway, which might be the case of KRAS-mutant non-small-cell lung cancers (NSCLCs). AZD 6244 33-44 mitogen-activated protein kinase 1 Homo sapiens 121-124 23320839-12 2013 MEK inhibitors U0126 and AZD6244 deactivated phosphorylated ERK, decreased endogenous MRP1 expression, reversed gemcitabine or doxorubicin induced MRP1 and MRP3 upregulation, and increased the intracellular doxorubicin accumulation. AZD 6244 25-32 mitogen-activated protein kinase 1 Homo sapiens 60-63 22641227-10 2012 Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-beta and ERK, p90RSK, p70S6K, cdk-2 and retinoblastoma. AZD 6244 10-17 mitogen-activated protein kinase 1 Homo sapiens 109-112 22821509-6 2012 Increased proliferation due to strong activation of extracellular-signal-regulated kinase 1/2 (ERK1/2) is caused by overexpression/activation of platelet-derived growth factor receptor-beta (PDGFR-beta) and ErbB2/3 which we successfully blocked with AZD6244, sorafenib, or lapatinib. AZD 6244 250-257 mitogen-activated protein kinase 1 Homo sapiens 52-93 22641227-0 2012 Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma. AZD 6244 33-40 mitogen-activated protein kinase 1 Homo sapiens 19-22 23372439-1 2012 Selumetinib (AZD6244, ARRY-142886) is a potent, selective, uncompetitive inhibitor of MEK 1 / 2, part of the RAF/MEK/ERK protein kinase signal cascade, which is responsible for tumor. AZD 6244 0-11 mitogen-activated protein kinase 1 Homo sapiens 117-120 22765220-11 2012 Inhibition of ERK signaling in MCF7-Six1 cells with MEK1/2 inhibitors, U0126 and AZD6244, restores the TIC population of luminal breast cancer cells back to that observed in control cells. AZD 6244 81-88 mitogen-activated protein kinase 1 Homo sapiens 14-17 22573716-3 2012 In 19 GBM cell lines, we found that treatment with the clinically available MEK inhibitors PD0325901 or AZD6244 decreased levels of phospho-ERK, the downstream effector of MEK, regardless of NF1 status. AZD 6244 104-111 mitogen-activated protein kinase 1 Homo sapiens 140-143 23372439-1 2012 Selumetinib (AZD6244, ARRY-142886) is a potent, selective, uncompetitive inhibitor of MEK 1 / 2, part of the RAF/MEK/ERK protein kinase signal cascade, which is responsible for tumor. AZD 6244 13-20 mitogen-activated protein kinase 1 Homo sapiens 117-120 23372439-1 2012 Selumetinib (AZD6244, ARRY-142886) is a potent, selective, uncompetitive inhibitor of MEK 1 / 2, part of the RAF/MEK/ERK protein kinase signal cascade, which is responsible for tumor. AZD 6244 22-33 mitogen-activated protein kinase 1 Homo sapiens 117-120 22275507-10 2012 Immunohistochemistry of tumor tissues revealed that selumetinib alone or with cediranib reduced ERK phosphorylation, angiogenesis, and tumor cell proliferation and increased apoptosis. AZD 6244 52-63 mitogen-activated protein kinase 1 Homo sapiens 96-99 21215703-5 2011 We further reveal that AZD6244, a clinical trial drug that inhibits RAF1-ERK signaling, could prevent breast cancer progression by eliminating BTICs. AZD 6244 23-30 mitogen-activated protein kinase 1 Homo sapiens 73-76 21628402-2 2011 The novel 2nd generation anti-MEK small molecule, AZD6244, down-regulated its direct downstream target, phospho-ERK (pERK) in germinal center and nongerminal center diffuse large B-cell lymphoma (DLBCL) cell lines and primary cells. AZD 6244 50-57 mitogen-activated protein kinase 1 Homo sapiens 112-115 21628402-4 2011 Consequently, several lymphoma-related ERK substrates were down-regulated by AZD6244 including MCT-1, c-Myc, Bcl-2, Mcl-1, and CDK1/2. AZD 6244 77-84 mitogen-activated protein kinase 1 Homo sapiens 39-42 21447798-3 2011 AZD6244-resistant derivatives were refractory to AZD6244-induced cell cycle arrest and death and exhibited a marked increase in ERK1/2 (extracellular signal-regulated kinases 1 and 2) pathway signaling and cyclin D1 abundance when assessed in the absence of inhibitor. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 136-182 21674991-4 2011 AZD6244-resistant derivatives were refractory to AZD6244-induced cell cycle arrest and death and exhibited a marked increase in ERK1/2 (extracellular signal-regulated kinases 1 and 2) pathway signaling and cyclin D1 abundance when assessed in the absence of inhibitor. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 136-182 21118963-6 2011 In contrast, AS703026 and AZD6244 effectively inhibited the growth of D-MUT cells in vitro and in vivo by specific inhibition of the key MEK downstream target kinase ERK. AZD 6244 26-33 mitogen-activated protein kinase 1 Homo sapiens 166-169 20101735-5 2010 RESULTS: We report here that pharmacological inhibition of the MEK/ERK pathway by AZD6244 enhanced the antitumor and antiangiogenic activities of mTOR inhibitor RAPA in both orthotopic and ectopic models of HCC. AZD 6244 82-89 mitogen-activated protein kinase 1 Homo sapiens 67-70 21098728-7 2010 In cell lines, BRAF amplification increased the abundance of phosphorylated MEK and impaired the ability of AZD6244 to inhibit ERK (extracellular signal-regulated kinase) phosphorylation. AZD 6244 108-115 mitogen-activated protein kinase 1 Homo sapiens 127-130 21098728-7 2010 In cell lines, BRAF amplification increased the abundance of phosphorylated MEK and impaired the ability of AZD6244 to inhibit ERK (extracellular signal-regulated kinase) phosphorylation. AZD 6244 108-115 mitogen-activated protein kinase 1 Homo sapiens 132-169 21098728-8 2010 The ability of AZD6244 to inhibit ERK phosphorylation in AR cells was restored by treatment with a BRAF inhibitor at low concentrations that reduced the abundance of phosphorylated MEK to amounts observed in parental cells. AZD 6244 15-22 mitogen-activated protein kinase 1 Homo sapiens 34-37 19548087-3 2009 AZD6244 effectively blocked AraC-induced MEK/ERK activation and enhanced its ability to induce growth arrest and apoptosis of NB4 and HL60 cells in parallel with induction of DNA damage as measured by detection of gamma-H2AX by Western Blot analysis, resulting in enhanced expression of p21( waf1 ) and downregulation of c-Myc and Bcl-xl in these cells. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 45-48 20103661-2 2010 AZD6244 blocks MEK1/2, inhibiting ERK phosphorylation. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 34-37 19783898-4 2009 Subsequent molecular characterization showed that treatment with AZD6244 suppressed ERK phosphorylation in both sensitive and resistant cells, suggesting that resistance is not mediated by the activities of MEK/ERK themselves. AZD 6244 65-72 mitogen-activated protein kinase 1 Homo sapiens 84-87 19910069-7 2010 Pharmacological inhibition of the MEK/ERK pathway by AZD6244 enhanced the anti-tumor effect of sorafenib in both orthotopic and ectopic models of HCC. AZD 6244 53-60 mitogen-activated protein kinase 1 Homo sapiens 38-41 18632602-6 2008 A selective MEK inhibitor, AZD6244, inhibits mutant-induced ERK activity in 293T cells and growth of mutant-bearing Ba/F3 cells. AZD 6244 27-34 mitogen-activated protein kinase 1 Homo sapiens 60-63 18676837-1 2008 AZD6244 (ARRY 142886) is a potent and selective mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor currently in early clinical trials. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 82-86 18676837-1 2008 AZD6244 (ARRY 142886) is a potent and selective mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor currently in early clinical trials. AZD 6244 0-7 mitogen-activated protein kinase 1 Homo sapiens 127-130 17878251-5 2007 RESULTS: AZD6244 potently inhibited MEK 1/2 activity in thyroid cancer cell lines regardless of BRAF mutation status, as evidenced by reduced ERK phosphorylation. AZD 6244 9-16 mitogen-activated protein kinase 1 Homo sapiens 142-145 17878251-10 2007 CONCLUSION: AZD6244 inhibits the MEK-ERK pathway across a spectrum of thyroid cancer cells. AZD 6244 12-19 mitogen-activated protein kinase 1 Homo sapiens 37-40