GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation With Favorable Pharmacokinetic Properties for Sustained in Vivo Pathway Inhibition

0 views | May 26 2020

Aidan G Gilmartin et al. fond that GSK1120212 combineed high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors. [Read the Full Post]

TFEB-mediated lysosomal biogenesis and lysosomal drug sequestration confer resistance to MEK inhibition in pancreatic cancer

51 views | Mar 25 2020

Zhao B et al. showed accumulation of MEKi in the lysosomes of treated cells. [Read the Full Post]

PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy in a cardiac arrest rat model

54 views | Feb 03 2020

Zheng JH et al. showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. [Read the Full Post]

MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway

61 views | Jan 30 2020

Nan P et al. found that MTA1 plays a pivotal oncogenic role in ESCC tumorigenesis and development through activating the MEK/ERK/p90RSK pathway. [Read the Full Post]

The small molecule AZD6244 inhibits dengue virus replication in vitro and protects against lethal challenge in a mouse model

62 views | Jan 30 2020

de Oliveira LC et al. demonstrated the potential of AZD6244 as a new therapeutic agent to treat DENV infection and possibly other flavivirus diseases. [Read the Full Post]

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFV600E by synergistically decreasing global trimethylation of H3K27

64 views | Jan 29 2020

Fu H et al. found that tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring BRAFV600E through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy. [Read the Full Post]

PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts

78 views | Nov 20 2019

Choo EF et al. suggested that, based on minimal data, it is possible to predict the effects of various combinations preclinically and also assess the potential clinical efficacy of combinations using human pharmacokinetic inputs. [Read the Full Post]

U0126 attenuates ischemia/reperfusion-induced apoptosis and autophagy in myocardium through MEK/ERK/EGR-1 pathway

110 views | Nov 20 2019

Wang A et al. suggested that U0126 may protect against H/R injury by preventing H/R-induced myocardium apoptosis and autophagy via the MEK/ERK/EGR-1 pathway, and may be a potential therapeutic approach for attenuating myocardial I/R injury. [Read the Full Post]

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity

82 views | Nov 05 2019

Bernstein A et al. found that Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events. [Read the Full Post]

Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab

81 views | Nov 04 2019

Moser JC et al. found that patients with advanced BRAF mutant melanoma treated with front-line niv/ipi or aPD-1 had longer survival compared to those treated with front-line BRAF/MEKi. [Read the Full Post]