Fig. 1

Effects of PPL008 conjugates on pERK levels and rate of cell proliferation. Normalised phospho-ERK (mean ± SEM) following treatment with DMSO (lane 1), PLX4032 B-Raf inhibitor (lane 2), PPL008 conjugates (lanes 11–14) or PLX co-treatments with PDE8A – C-Raf peptide disrupters (original stearylated ‘disrupter’ lane 3, or scrambled control, lane 4) or PPL-008 conjugates (lanes 7–10) in: a MM415 (NRAS Q61L) and (b) A375 (BRAF V600E) human malignant melanoma cell lines. Respective pERK and GAPDH immunoblot examples shown below (N ≥ 3, * P < 0.05, ** P < 0.01). c Real-time cell analyses (xCELLigence platform) of MM415 cell proliferation following treatments described above. Treatments occurred at 21 h and the slope of normalised cell index (mean ± STDEV) was measured between 21 and 39 h, with (ii) representing DMSO vs. peptide disrupter treatments only (10 μM) and (iii) representing PLX (1 μM) vs. co-treatments of peptide disrupters and PLX4032 (n = 3, *** P < 0.001). D, stearylated disrupter; S, stearylated scrambled; N, PPL-008 N; C, PPL-008C; NSS, PPL-008NSS; CSS, PPL-008CSS