Az138

AZ304 and AZ138 were synthesised at AstraZeneca plc (London, UK). Cetuximab was obtained from Merck KgaA (Darmstadt, Germany). EGF was obtained from Pepro Tech (Rocky, USA), Antibodies of p-EGFR (Tyr1068) (2234 S), EGFR (2646 S), BRAF (4933 S), p-ERK1/2 (Thr202/Tyr204) (4370 S), p-p38 (Thr180/Tyr182) (9216 S), p38 (9218 S), p-AKT (Ser473) (4060 S), AKT (9272 S), p-mTOR (Ser2448) (2971 S), SRC (2109 S), p-SRC (Y416) (6943 S), STAT3 (4904 S), p-STAT3 (Tyr705) (9145 S), Caspase-9 (9508 S), Caspase-3 (9662 S) and PARP (9542 L) were obtained from Cell Signalling Technology (Danvers, MA, USA). Antibody of ERK (sc-514302), Actin (sc-1616-R), mTOR (sc-1550-R), goat anti-rabbit IgG and goat anti-mouse IgG were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Anti-Ki67 antibody was purchased from Fuzhou Maixin Biological Technology (Fujian, China).

The following drugs were dissolved in DMSO and stored at −20°C: WEHI-539 [32 (link)] (Apexbio); taxol (Sigma); nocodazole (Sigma); AZ138 [8 (link)] (AstraZeneca)); AZ3146 [43 (link)] (AstraZeneca); BI 2536 [38 (link)] (Boehringer Ingelheim); GSK923295 [39 (link),70 ]; MLN8054 [41 (link)] (Millennium Pharmaceuticals); ZM447439 [42 (link)] (Tocris); A-1210477 [31 (link)] (Medchemexpress). Tetracycline (Sigma) was dissolved in water, stored at −20°C, and used at concentrations indicated in the figure legends. Thymidine (Sigma) was dissolved in PBS at a concentration of 200 mM, and stored short-term at 4°C.