1. 00.111000.1110 A375A375R2 Vemurafenib (µM) BRAF (Full Length) p61-BRAF Isoform pMEK pERK Tubulin Supplementary Figure S1 0.004.01.040.01.030.10.313100.01.11 A375-R4 NRas Q61KA375 Vemurafenib (µM) pMEK pS338-cRaf pERK Ras Tubulin B A

2. Supplementary Figure S2 Vehicle Vemurafenib LY2835219 Vemurafenib

3. Supplementary Figure S3 A375A375-RV2 pERK Tubulin Vemurafenib (µM)

4. Supplementary Figure S4 DMSO 1.5  M  M M14 M14-R %G1= 54.25 %S = 34.96 %G2/M = 10.79 %G1= 82.10 %S = 2.73 %G2/M = 15.17 %G1= 74.95 %S = 3.81 %G2/M = 21.24 %G1= 55.23 %S = 13.34 %G2/M = 31.43 %Debris = 41.73 %G1= 38.71 %S = 35.28 %G2/M = 26.02 %Debris = 72.17 %G1= 58.58 %S = 24.88 %G2/M = 16.54 LY2835219 0 50 100 150 200 250 300 0.02.63.03.54.0 Relative Caspase 3 Activity (%) Log Concentration LY2835219 (nM) A375 A375-R1 M14 M14-R B A A375A375-RV1A375-RV2A375-R1A375A375-RV1A375-RV2A375-R1 Cyclin D1 siRNA Cyclin D1 ←Cyclin D2 Cleaved-PARP Tubulin C