Results 11 to 20 of about 130,251 (209)

Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation

Proceedings of the National Academy of Sciences, 2021
Significance Drugs that inhibit specific kinases now represent one of the main classes of targeted therapies. A majority of drug development efforts in this space focus on a given kinase in isolation as the target. However, our work demonstrates that in the context of the RAF/MEK/ERK pathway, the relevant target for compounds developed as ...
Gonzalo L. Gonzalez-Del Pino, Kunhua Li, Eunyoung Park, Anna M. Schmoker, Byung Hak Ha, Michael J. Eck   +5 more
openaire   +3 more sources

MEK Inhibitor-Associated Ocular Hypertension. [PDF]

Ocul Oncol Pathol, 2023
<b><i>Introduction:</i></b> Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anticancer agents that are prescribed to treat a broad range of cancers. Despite their strong efficacy profile, MEK inhibitors have been associated with ocular toxicities, most notably, self-limited serous detachments of the ...
Collet DA, Canestraro J, Abou-Alfa GK, Abramson DH, Diamond EL, Francis JH.   +5 more
europepmc   +3 more sources

Emerging MEK inhibitors

Expert Opinion on Emerging Drugs, 2010
The Ras/Raf/MEK/ERK pathway is often activated by genetic alterations in upstream signaling molecules. Integral components of this pathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/MEK/ERK pathway has profound effects on proliferative, apoptotic and differentiation pathways.
McCubrey JA, Steelman LS, Abrams SL, Chappell WH, Russo S, Ove R, Milella M, Tafuri A, Lunghi P, Bonati A, Stivala F, NICOLETTI, FERDINANDO, LIBRA, Massimo, Martelli AM, Montalto G, Cervello M.   +15 more
openaire   +5 more sources

Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP [PDF]

, 1999
Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types.
A Minden, A Sewing, AD Catling, B Hallberg, CJ Marshall, D Woods, DK Grandy, DK Morrison, DW Rose, F Schoentgen, Ferrell, J. E. Jr, Ferrell, J. E. Jr, H Mischak, HJ Schaeffer, JT Bruder, KL Guan, M Kortenjann, OV Gjorup, RM Lavbinsky, RM Tombes, S Häfner, S Li, SA Moodie, UR Rapp, W Kolch, W Kolch   +25 more
core   +1 more source

Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer

Acta Pharmaceutica Sinica B, 2023
MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to ...
Juanjuan Feng, Zhengke Lian, Xinting Xia, Yue Lu, Kewen Hu, Yunpeng Zhang, Yanan Liu, Longmiao Hu, Kun Yuan, Zhenliang Sun, Xiufeng Pang   +10 more
doaj   +1 more source

Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model. [PDF]

, 2016
Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients ...
Berger, Mitchel S, Daynac, Mathieu, Grossauer, Stefan, James, C David, Koeck, Katharina, McMahon, Martin, Meyers, Ian D, Murphy, Nicole E, Nicolaides, Theodore P, Petritsch, Claudia K, Phillips, Joanna J, Truffaux, Nathalene, Truong, Albert Y   +12 more
core   +1 more source

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis [PDF]

, 2015
Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to ...
AA Eddy, Arif Khwaja, B Conway, B Hinz, C Stambe, D Bokemeyer, D Bokemeyer, D Feliers, David Long, DY Rhyu, E Diaz-Flores, Faith Hannah Nutter, FY Ma, FY Ma, FY Ma, G Wolf, GA Reif, GM D'Abaco, H Fujita, H Ha, H Tamouza, HJ Anders, J Chen, John L. Haylor, JW Pippin, JY Seo, L Aoudjit, LF Allen, LL Huang, M Peake, M Sabbatini, M Zeisberg, MA Chetram, MH De Borst, N Sakai, P Moreno-Layseca, PM Lorusso, R Ohashi, R Roskoski Jr, S Omori, S Wang, S Wang, SD Oldroyd, SK Jo, SP Davies, T Ishida, T Masaki, T Wada, T Xu, W Bechtel, Y Han   +50 more
core   +2 more sources

Outcomes of patients with advanced cancer and KRAS mutations in phase I clinical trials. [PDF]

, 2014
BackgroundKRAS mutation is common in human cancer. We assessed the clinical factors, including type of KRAS mutation and treatment, of patients with advanced cancer and tumor KRAS mutations and their association with treatment outcomes.MethodsPatients ...
Aldape, Kenneth, Blumenschein, George R, Falchook, Gerald Steven, Fu, Siqing, Hess, Kenneth R, Hong, David S, Janku, Filip, Kurzrock, Razelle, Naing, Aung, Palmer, Gary A, Piha-Paul, Sarina Anne, Said, Rabih, Tsimberidou, Apostolia Maria, Wheler, Jennifer J, Ye, Yang, Zinner, Ralph   +15 more
core   +4 more sources

Hypoxia sustains glioblastoma radioresistance through ERKs/DNA-PKcs/HIF-1α functional interplay [PDF]

, 2014
The molecular mechanisms by which glioblastoma multiforme (GBM) refracts and becomes resistant to radiotherapy treatment remains largely unknown. This radioresistance is partly due to the presence of hypoxic regions, which are frequently found in GBM ...
Cerasani, Manuela, Ciccarelli, Carmela, Di Cesare, Ernesto, Di Genova, Daniela, Festuccia, Claudio, Ficorella, Corrado, Fratticci, Amato, Gravina, Giovanni Luca, Mancini, Marta, Marampon, Francesco, Popov, Vladimir M, Zani, Bianca Maria   +11 more
core   +1 more source

BRAF Splice Variant Resistance to RAF Inhibitor Requires Enhanced MEK Association

Cell Reports, 2018
Summary: Expression of aberrantly spliced BRAF V600E isoforms (BRAF V600E ΔEx) mediates resistance in 13%–30% of melanoma patients progressing on RAF inhibitors. BRAF V600E ΔEx confers resistance, in part, through enhanced dimerization.
Michael J. Vido, Kaitlyn Le, Edward J. Hartsough, Andrew E. Aplin   +3 more
doaj   +1 more source