Caspase 3‐specific cleavage of MEK1 suppresses ERK signaling and sensitizes cells to stress‐induced apoptosis
Sign Up to like & getrecommendations! Published in 2023 at "FEBS Open Bio"
DOI: 10.1002/2211-5463.13574
Abstract: Proper regulation of apoptotic cell death is crucial for normal development and homeostasis in multicellular organisms and is achieved by the balance between pro‐apoptotic processes, such as caspase activation, and pro‐survival signaling, such as extracellular… read more here.
Keywords: apoptosis; stress induced; erk; mek1 ... See more keywords
Phase II study of selumetinib, an orally active inhibitor of MEK1 and MEK2 kinases, in KRASG12R-mutant pancreatic ductal adenocarcinoma
Sign Up to like & getrecommendations! Published in 2021 at "Investigational New Drugs"
DOI: 10.1007/s10637-020-01044-8
Abstract: Background Preclinical evidence has suggested that a subset of pancreatic cancers with the G12R mutational isoform of the KRAS oncogene is more sensitive to MAPK pathway blockade than pancreatic tumors with other KRAS isoforms. We… read more here.
Keywords: inhibitor; orally active; study; selumetinib orally ... See more keywords
Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases
Sign Up to like & getrecommendations! Published in 2023 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.3c00014
Abstract: The ERK pathway is one of the most important signaling cascades involved in tumorigenesis. So far, eight noncovalent inhibitors of RAF and MEK kinases in the ERK pathway have been approved by the FDA for… read more here.
Keywords: erk pathway; raf mek; analysis; covalent ... See more keywords
Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c02192
Abstract: Mutations in MEK1/2 have been described as a resistance mechanism to BRAF/MEK inhibitor treatment. We report the discovery of a novel ATP-competitive MEK1/2 inhibitor with efficacy in wildtype (WT) and mutant MEK12 models. Starting from… read more here.
Keywords: selective mek1; inhibitor; mek1 inhibitor; atp competitive ... See more keywords
Discovery of a First-in-class Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Degrader.
Sign Up to like & getrecommendations! Published in 2019 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.9b01528
Abstract: MEK1 and MEK2 (also known as MAP2K1 and MAP2K2) are the "gatekeepers" of the ERK signaling output with redundant roles in controlling ERK activity. Numerous inhibitors targeting MEK1/2 have been developed including three FDA-approved drugs.… read more here.
Keywords: degrader; kinase; discovery first; mek1 ... See more keywords
Discovery of Coumarin-Based MEK1/2 PROTAC Effective in Human Cancer Cells.
Sign Up to like & getrecommendations! Published in 2022 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.2c00446
Abstract: The RAF/MEK/ERK pathway is a crucial signal path which is closely associated with the proliferation, differentiation, and apoptosis of tumors. MEK1/2 is a key kinase target in the pathway, with ERK1/2 acting as the main… read more here.
Keywords: effective human; protac effective; human cancer; mek1 ... See more keywords
Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.
Sign Up to like & getrecommendations! Published in 2021 at "Cerebral cortex"
DOI: 10.1093/cercor/bhaa413
Abstract: Many developmental syndromes have been linked to genetic mutations that cause abnormal ERK/MAPK activity; however, the neuropathological effects of hyperactive signaling are not fully understood. Here, we examined whether hyperactivation of MEK1 modifies the development… read more here.
Keywords: hyperactive mek1; mek1 signaling; neuron; parvalbumin ... See more keywords
P1936Selective inhibition of the Mek1/2-Erk1/2 signalling pathway induces the differentiation of human cardiac pericyte-like cells into contractile vascular smooth muscle cells
Sign Up to like & getrecommendations! Published in 2019 at "European Heart Journal"
DOI: 10.1093/eurheartj/ehz748.0683
Abstract: Arteriogenesis is key for tissue repair but whether myocardial stromal cells contribute to this phenomenon remains unknown. Investigate if cardiac pericytes are a druggable target for therapeutic arteriogenesis. The localization of pericyte-like cells (PCs) was… read more here.
Keywords: pericyte like; like cells; pcs; mek1 erk1 ... See more keywords
MicroRNA-181a-5p prevents the progression of esophageal squamous cell carcinoma in vivo and in vitro via the MEK1-mediated ERK-MMP signaling pathway.
Sign Up to like & getrecommendations! Published in 2022 at "Aging"
DOI: 10.18632/aging.204028
Abstract: MicroRNAs (miRNAs) have been revealed to play a crucial role in oncogenesis of esophageal squamous cell carcinoma (ESCC). However, the biological role of miR-181a-5p in ESCC is currently less explored. The current study was designed… read more here.
Keywords: 181a mimics; progression; mek1; erk mmp ... See more keywords
Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells
Sign Up to like & getrecommendations! Published in 2017 at "Oncotarget"
DOI: 10.18632/oncotarget.20408
Abstract: A critical problem in leukemia as well as other cancer therapies is the development of chemotherapeutic drug-resistance. We have developed models of hematopoietic drug resistance that are based on expression of dominant-negative TP53 [TP53 (DN)]… read more here.
Keywords: drug resistance; resistance; tp53; mek1 ... See more keywords
Mek1 and Mek2 Functional Redundancy in Erythropoiesis
Sign Up to like & getrecommendations! Published in 2021 at "Frontiers in Cell and Developmental Biology"
DOI: 10.3389/fcell.2021.639022
Abstract: Several studies have established the crucial role of the extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase pathway in hematopoietic cell proliferation and differentiation. MEK1 and MEK2 phosphorylate and activate ERK1 and ERK2. However, whether MEK1 and… read more here.
Keywords: mek2 functional; mek1 mek2; redundancy; mek1 ... See more keywords