Gsk1838705a

The H1944 or A549 cells were trypsinised and resuspended in PBS at a density of six (H1944) or two (A549) million cells/50 µl and mixed with an equal volume of BME (#3533-005-02, Sigma-Aldrich) NOD-scid-γ (NSG) mice (±7 weeks old) were anesthetised before injection of six million cells subcutaneously into one of the flanks. Once the tumour size reached between 100 and 300 mm³ the mice were treated with 4 mg/kg dexamethasone (D2915-100MG, Sigma-Aldrich; dissolved in water), 75 (H1944) and 20 (A549) mg/kg Linsitinib (HY-10191, MedChemExpress; dissolved in 25 mM tartaric acid), 25 mg/kg GSK1838705A (MedChemExpress; dissolved in 20% sulfobutyl ether β-cyclodextrin (ISP; pH 3.5)), combination, or vehicle by I.P. injections (dexamethasone) and orally (IGF-1R inhibitors) on a daily basis. Tumour volume was monitored by calliper measurements every 2 days. Mice were kept under standard temperature and humidity conditions in individually ventilated cages, with food and water provided ad libitum. The NKI Animal Experiments Committee approved all in vivo experiments (project number 9139 and 9907).

Dabrafenib and trametinib were purchased from LC Laboratories. BMS-754807, Linsitinib, BMS-536924, and GSK1838705A were purchased from MedChemExpress. SCH772984 was obtained from Selleckchem (Houston, TX, USA). All drugs were dissolved in DMSO (Fisher Scientific(Waltham, MA, USA)) at described concentrations and stored at −20 $$℃$$ . IGF2 (cat#100-12) was purchased from Peprotech (Cranbury, NJ, USA).