Amongst the investigated inhibitors, tumor cells harboring C228T mutation were distinctly more sensitive against trametinib as compared to TERTwt and C250T TERTmut cells. Similar effects were observed on clonogenicity upon long-term exposure to this inhibitor. Regarding MAPK signaling activation, ...
2. Results 2.1. Vemurafenib Treatment Affects Cytokine Secretion and Expression of Maturation Markers on MoDCs To assess the effects of BRAF and MEK inhibitor (BRAFi/MEKi) treatment on moDC maturation, we applied vemurafenib (vemu, V), dabrafenib (dabra, D), trametinib (tram, T), and cobim...
E1902NewNedometinibNedometinib (NFX-179) is a highly specific and potent inhibitor ofMEK1with an IC50 of 135 nM. It also results in suppression ofp-ERKlevels and can be used in research and treatment of cutaneous neurofibromas (cNFs) associated with neurofibromatosis type 1 (NF1). ...
Direct anti-proliferative effects of sunitinib plus MEK inhibitor were assessed. Activation status (phosphorylation) of MEK1/2 and ERK1/2 was determined, myeloid- derived suppressor cells (MDSC) sub-fractions were quantitated and G-CSF was measured by ELISA. Results: During the response phase, ...
WX-554 is planned to be administered intravenously as single doses in the range of 0.05 mg/kg to 5.0 mg/kg to healthy volunteers in dose escalated manner [102]. Results of this study are not available yet. An oral formulation of this inhibitor is being tested in a phase I/II trial in...
The above results prompted us to confirm that the disappearance of IκB-α that results from the overexpression of MEK kinase is due to the enhanced degradation of IκB-α. To address this issue, calpain inhibitor-I, a reported inhibitor of IκB-α degradation (15, 16), was used. Treatme...
(Fig.2e, middle). Moreover, treatment with proteasome inhibitor (MG132) restored the endogenous GLI1 protein levels in MEKK3 overexpression NIH3T3 cells (Supplementary FigureS2c). To further understand how MEKK2/3 control GLI1 activity, we asked whether the phosphorylation status of GLI1 ...
Results KRAS Mutant Cancer Cell Lines Are Unresponsive to MEK Inhibitors To study how KRAS mutant cancer cells respond in vitro to MEK inhibition, we determined the efficacy of the MEK inhibitor selumetinib (AZD6244) in four NSCLC and four colon cancer cell lines using a long-term proliferation...
BMC Medicine (2023) 21:2 https://doi.org/10.1186/s12916-022-02669-7 RESEARCH ARTICLE Open Access First‑in‑human phase I dose‑escalation and dose‑expansion trial of the selective MEK inhibitor HL‑085 in patients with advanced melanoma harboring NRAS mutations Xuan Wang...
Results Trametinib exerts a strong antiproliferative effect on Glioblastoma (GB) cell lines First, we evaluated the effect of the highly specific MEK1/2 inhibitor Trametinib on the metabolic activity of two established GB cell lines, A172 and U87MG (Fig. 1A). As Trametinib exposure at a concen...