Gene expression profiling of melanoma cell lines (carrying NF1 loss-of-function) treated with DMSO (vehicle), MTX-216, MTX-211, trametinib, the combination of MTX-216 and trametinib, or pictilisib

In this study, we identified a multi-kinase inhibitor MTX-216 to be efficacious in blocking NF1 loss-of-function melanoma cells. To identify the mechansisms of action of MTX-216, we treated NF1 loss-of-function melanoma cell lines with MTX-216, MTX-211 (the structural analogue of MTX-216 that has no effect on melanoma cells) as well as commericial kinase inhibitors, trametinib and pictilisib, and compared their gene expression profiles. Overall design: Three NF1 loss-of-function melanoma cell lines (MeWo, WM3918, SKMEL113) were treated with MTX-216 (1 uM), MTX-211 (1 uM), trametinib (0.1 uM), the combination of MTX-216 (1 uM) and trametinib (0.1 uM), pictilisib (1 uM), or DMSO (control) for 24 hours. Samples were treated in three independent replicates. Samples were enriched for polyA RNA prior to sequencing. Samples were run on Illumina NovaSeq 6000 (S4) using paired-end read with 150 cycles. In total, 1.4 billion reads were generated, including ~33 million reads per sample.