PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 27422710-6 2016 Moreover, selumetinib reduced inhibitory serine phosphorylation of MET at Ser985 and potentiated HGF- and EGF-induced AKT phosphorylation. AZD 6244 10-21 AKT serine/threonine kinase 1 Homo sapiens 118-121 35523987-6 2022 Through protein interaction (PPI), gene enrichment analysis, and gene difference analysis, one effective target of Selumetinib was finally screened, CDK2 mainly existing in the cytoplasm, endoplasmic reticulum, and plasma membrane; the target plays a role in the treatment of LGG by inhibiting the signal pathways of PI3K Akt and participating in biological processes such as peptide amino acid modification, regulation of intracellular signal transduction, and positive regulation of cell metabolism. AZD 6244 115-126 AKT serine/threonine kinase 1 Homo sapiens 322-325 33416182-5 2021 Despite the different levels of sensitivity, Selumetinib mediated the phosphorylation of AKT and MEK in both cell lines and suppressed the phosphorylated MAPK cascades. AZD 6244 45-56 AKT serine/threonine kinase 1 Homo sapiens 89-92 29928418-7 2018 Inhibition of EGFR activity using cetuximab partially abrogated the feedback-activation of phosphorylated receptor tyrosine-protein kinase erB-3 (p-HER3) and p-AKT serine/threonine kinase (AKT), as well as prevented reactivation of p-extracellular regulated kinase (ERK) conferred by AZD6244 treatment. AZD 6244 284-291 AKT serine/threonine kinase 1 Homo sapiens 160-163 29928418-8 2018 Combination of AZD6244 and cetuximab also inhibited HT29 cell xenograft growth in nude mice and suppressed HER3 and p-AKT levels in xenografts. AZD 6244 15-22 AKT serine/threonine kinase 1 Homo sapiens 118-121 34666331-3 2021 Hence, we aimed to initially explore the mechanism of AKT activation and observe the synergistic inhibitory effect of combining AKT (MK-2206) and MAPK kinase (AZD 6244) inhibitors in MARIMO cells. AZD 6244 159-167 AKT serine/threonine kinase 1 Homo sapiens 54-57 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 AKT serine/threonine kinase 1 Homo sapiens 23-26 30021885-7 2018 Treatment with an orally bioavailable small-molecule activator of PP2A DT-061, in combination with the MEK inhibitor AZD6244, resulted in suppression of both p-AKT and MYC, as well as tumor regression in two KRAS-driven lung cancer mouse models. AZD 6244 117-124 AKT serine/threonine kinase 1 Homo sapiens 160-163 28982310-7 2017 Wortmannin decreased phosphorylated adenosine monophosphate-activated protein kinase protein levels, and AZD6244 increased phosphorylated Akt protein levels. AZD 6244 105-112 AKT serine/threonine kinase 1 Homo sapiens 138-141 26601868-7 2016 This knowledge has led to the rational development of clinical trials specifically for UM utilizing targeted inhibitors of the activated signaling pathways such as mitogen-activated protein kinase, Akt, and protein kinase C. A recent trial of the oral MEK inhibitor selumetinib was the first to show clinical benefit for any systemic therapy in a randomized fashion. AZD 6244 266-277 AKT serine/threonine kinase 1 Homo sapiens 198-201 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 AKT serine/threonine kinase 1 Homo sapiens 133-136 25959272-6 2015 This effect was associated with an almost complete suppression of ERK1/2 activation and a reduction of selumetinib-induced AKT phosphorylation. AZD 6244 103-114 AKT serine/threonine kinase 1 Homo sapiens 123-126 25959272-8 2015 Taken together, our data demonstrated that blockade of the EGFR might efficiently increase the antitumor activity of selumetinib in a subgroup of TNBC and that this phenomenon might be related to the effects of such combination on both ERK1/2 and AKT activation. AZD 6244 117-128 AKT serine/threonine kinase 1 Homo sapiens 247-250 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 AKT serine/threonine kinase 1 Homo sapiens 65-68 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 AKT serine/threonine kinase 1 Homo sapiens 96-99 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 AKT serine/threonine kinase 1 Homo sapiens 56-59 25342139-8 2015 At the molecular level, we found that AKT activation strongly influenced the sensitivity of KRAS-mutant NSCLC cells to selumetinib. AZD 6244 119-130 AKT serine/threonine kinase 1 Homo sapiens 38-41 25342139-9 2015 Selumetinib upregulated phospho-AKT and phosphorylated BAD at ser136, which is responsible for intrinsic drug resistance in KRAS-mutant NSCLC cells. AZD 6244 0-11 AKT serine/threonine kinase 1 Homo sapiens 32-35 25342139-10 2015 In contrast, inhibition of the PI3K/AKT pathway by BYL719 hindered selumetinib-induced BAD phosphorylation and increased the antitumor efficacy of selumetinib. AZD 6244 67-78 AKT serine/threonine kinase 1 Homo sapiens 36-39 25342139-10 2015 In contrast, inhibition of the PI3K/AKT pathway by BYL719 hindered selumetinib-induced BAD phosphorylation and increased the antitumor efficacy of selumetinib. AZD 6244 147-158 AKT serine/threonine kinase 1 Homo sapiens 36-39 25342139-12 2015 On analysis of the pharmacodynamics, selumetinib and BYL719 together resulted in effective inhibition of both p-ERK and p-AKT expression in tumor tissue. AZD 6244 37-48 AKT serine/threonine kinase 1 Homo sapiens 122-125 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 AKT serine/threonine kinase 1 Homo sapiens 109-112 26137449-4 2015 Selumetinib and vemurafenib potently inhibited cell proliferation in all cell lines, especially in those that expressed low levels of phosphorylated AKT (pAKT). AZD 6244 0-11 AKT serine/threonine kinase 1 Homo sapiens 149-152 23443802-3 2013 In this study, using a siRNA strategy, we show that mutant GNAQ signals to both MEK and AKT, and that combined inhibition of these pathways with the MEK inhibitor selumetinib (AZD6244) and the AKT inhibitor MK2206 induced a synergistic decrease in cell viability. AZD 6244 163-174 AKT serine/threonine kinase 1 Homo sapiens 88-91 23444215-1 2013 PURPOSE: Test the hypothesis that in BRAF-mutated melanomas, clinical responses to selumetinib, a MEK inhibitor, will be restricted to tumors in which the PI3K/AKT pathway is not activated. AZD 6244 83-94 AKT serine/threonine kinase 1 Homo sapiens 160-163 21628402-0 2011 The novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse large B-cell lymphoma. AZD 6244 34-41 AKT serine/threonine kinase 1 Homo sapiens 68-71 22082529-1 2012 Previously, we found that KRAS mutant cancer cells showed variable response to AZD6244, a MEK inhibitor through differential activation of EGFR/AKT. AZD 6244 79-86 AKT serine/threonine kinase 1 Homo sapiens 144-147 22082529-3 2012 We found that treatment with AZD6244 reduced the expression of mitogen-inducible gene 6 (MIG6), a negative feedback regulator for EGFR, in AZD6244-resistant cells, while activity of EGFR and AKT was increased in these cells. AZD 6244 29-36 AKT serine/threonine kinase 1 Homo sapiens 191-194 22090271-0 2012 The Akt inhibitor MK2206 synergizes, but perifosine antagonizes, the BRAF(V600E) inhibitor PLX4032 and the MEK1/2 inhibitor AZD6244 in the inhibition of thyroid cancer cells. AZD 6244 124-131 AKT serine/threonine kinase 1 Homo sapiens 4-7 21828154-9 2011 The Akt inhibitor MK2206 sensitized BRAF-mutant cells to both PLX4720 and AZD6244 and sensitized Galpha-mutant cells to AZD6244 but did not overcome the resistance of the Galpha-mutant cells to PLX4720. AZD 6244 74-81 AKT serine/threonine kinase 1 Homo sapiens 4-7 21828154-9 2011 The Akt inhibitor MK2206 sensitized BRAF-mutant cells to both PLX4720 and AZD6244 and sensitized Galpha-mutant cells to AZD6244 but did not overcome the resistance of the Galpha-mutant cells to PLX4720. AZD 6244 120-127 AKT serine/threonine kinase 1 Homo sapiens 4-7 21124782-1 2010 AZD6244 and MK2206 are targeted small-molecule drugs that inhibit MEK and AKT respectively. AZD 6244 0-7 AKT serine/threonine kinase 1 Homo sapiens 74-77 21124782-3 2010 Our previous work showed the importance of activated AKT in mediating resistance of non-small cell lung cancer (NSCLC) to AZD6244. AZD 6244 122-129 AKT serine/threonine kinase 1 Homo sapiens 53-56 21124782-12 2010 The AZD6244-MK2206 combination therapy resulted in effective inhibition of both p-ERK and p-AKT expression in tumor tissue. AZD 6244 4-11 AKT serine/threonine kinase 1 Homo sapiens 92-95 20885957-10 2010 These results show that Bim plays an important role in AZD6244-induced apoptosis in lung cancer cells and that the PI3K/AKT/FOXO3a pathway is involved in Bim regulation and susceptibility of lung cancer cells to AZD6244. AZD 6244 212-219 AKT serine/threonine kinase 1 Homo sapiens 120-123 20959481-0 2010 Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells. AZD 6244 83-90 AKT serine/threonine kinase 1 Homo sapiens 42-45 20959481-7 2010 RPPA characterization of the time-dependent changes in signaling pathways revealed that AZD6244 produced durable and potent inhibition of P-MAPK in sensitive and resistant Braf-mutant cell lines, but several resistant lines showed AZD6244-induced activation of AKT. AZD 6244 88-95 AKT serine/threonine kinase 1 Homo sapiens 261-264 20959481-7 2010 RPPA characterization of the time-dependent changes in signaling pathways revealed that AZD6244 produced durable and potent inhibition of P-MAPK in sensitive and resistant Braf-mutant cell lines, but several resistant lines showed AZD6244-induced activation of AKT. AZD 6244 231-238 AKT serine/threonine kinase 1 Homo sapiens 261-264 20959481-9 2010 Inhibition of AKT, TORC1/2, or insulin-like growth factor I receptor blocked AZD6244-induced activation of AKT and resulted in synergistic cell killing with AZD6244. AZD 6244 77-84 AKT serine/threonine kinase 1 Homo sapiens 14-17 20959481-9 2010 Inhibition of AKT, TORC1/2, or insulin-like growth factor I receptor blocked AZD6244-induced activation of AKT and resulted in synergistic cell killing with AZD6244. AZD 6244 77-84 AKT serine/threonine kinase 1 Homo sapiens 107-110 20959481-9 2010 Inhibition of AKT, TORC1/2, or insulin-like growth factor I receptor blocked AZD6244-induced activation of AKT and resulted in synergistic cell killing with AZD6244. AZD 6244 157-164 AKT serine/threonine kinase 1 Homo sapiens 14-17 20959481-10 2010 These findings identify basal and treatment-induced regulation of the PI3K-AKT pathway as a critical regulator of AZD6244 sensitivity in Braf-mutant cutaneous melanoma cells and the novel regulation of PTEN expression by AZD6244 in sensitive cells, and suggest new combinatorial approaches for patients. AZD 6244 114-121 AKT serine/threonine kinase 1 Homo sapiens 75-78 20885957-9 2010 In addition, we found that transfection of constitutively active AKT up-regulated p-Thr32-FOXO3a and p-Ser253-FOXO3a expression and inhibited AZD6244-induced Bim expression in sensitive cells. AZD 6244 142-149 AKT serine/threonine kinase 1 Homo sapiens 65-68 19783898-0 2009 High level of AKT activity is associated with resistance to MEK inhibitor AZD6244 (ARRY-142886). AZD 6244 74-81 AKT serine/threonine kinase 1 Homo sapiens 14-17 19783898-0 2009 High level of AKT activity is associated with resistance to MEK inhibitor AZD6244 (ARRY-142886). AZD 6244 83-94 AKT serine/threonine kinase 1 Homo sapiens 14-17 19783898-6 2009 Stable transfection of dominant-negative AKT into resistant cells by retroviral infection restored their susceptibility to AZD6244. AZD 6244 123-130 AKT serine/threonine kinase 1 Homo sapiens 41-44 19783898-7 2009 These results indicate that phosphorylated AKT may be a biomarker of response to AZD6244 and that modulation of AKT activity may be a useful approach to overcome resistance to MEK inhibitors. AZD 6244 81-88 AKT serine/threonine kinase 1 Homo sapiens 43-46 19755509-7 2009 The results from Western blots and phosphoprotein arrays showed that, in MEK inhibitor resistant cell lines, AKT was activated through the EGFR/HER3/PI3K pathway following AZD6244 (ARRY-142886) treatment. AZD 6244 172-179 AKT serine/threonine kinase 1 Homo sapiens 109-112