Tumour cells with BRAF (most frequently BRAFV600E) or KRAS mutations are addicted to MEK1/2 (MAPK or ERK Kinase)–ERK1/2 (extracellular signal-regulated kinase) signalling for their proliferation, survival and other malignant properties. BRAF inhibitors (BRAFis) and allosteric MEK1/2 inhibitors...
Drug or vehicle solvent was added to the cell suspension before plating the cells. The assay was performed in triplicate and each plate had quadruple positive (UBB) and negative (GAPDH) controls. After 96h incubation at 37°C with 5% CO2, the number of viable cells in each well was ...
the ester with an excess of the appropriate aniline neat or in an organic solvent like xylenes. For example, when R1=Me and R2=H the preferred method is stirring the ester with 10 equivalents aniline in xylenes at reflux until complete reaction. In step 5, the nitro arene is reduced to ...
Column chromatography was performed using 200-300 mesh silica with the proper solvent system according to TLC analysis using KMnO4 stain and UV light to visualize the reaction components. Unless otherwise noted, 1H-NMR (400 MHz), 19F-NMR spectra (376 MHz) were recorded at ambient temperature ...