Linsitinib (Synonyms: OSI 906; OSI-906; OSI906)

Cell lines

HepG2, Hep3B, Huh-7, PLC/PRF/5, SNU-387 and SNU-423 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

3 μM, 20 hours

Applications

All 6HCCcell lines showed higher IR phosphorylation than IGF-1R, suggesting the significance of IR activity in HCC. Furthermore, all 3 HCC cell lines (HepG2, Hep3B, and HuH-7) that are sensitive to OSI-906 had much higher phosphorylation levels of both IGF-1R and IR than insensitive cell lines. This suggests that sensitivity to OSI-906 associates with activation of both IGF-1R and IR in HCC cell lines.

Animal models

Female athymic nude mice injected with NCI-H292 or NCI-H441 cells

Dosage form

Oral administration, 60 mg/kg

Applications

The NCI-H292 xenografts (sensitive to OSI-906 treatment) show a significant decrease (p<0.05) in 18FDG uptake at 2, 4 and 24 hours post dosing with OSI-906 compared to vehicle treated controls. NCI-H441 xenografts (insensitive to OSI-906 treatment) did not demonstrate a significant change in uptake of 18FDG at any time point evaluated. The decreased %ID/g in the NCI-H292 xenografts is suggestive of a rapid PD effect observed by 18FDG imaging mediated by the inhibition of IGF-1R and IR pathways by OSI-906. Conversely, for the NCI-H441 xenograft model no difference in uptake of the radiotracer was observed in the tumor samples between vehicle controls and the OSI-906 treatment group.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Zhao H, Desai V, Wang J, et al. Epithelial–Mesenchymal Transition Predicts Sensitivity to the Dual IGF-1R/IR Inhibitor OSI-906 in Hepatocellular Carcinoma Cell Lines. Molecular cancer therapeutics, 2012, 11(2): 503-513.

[2] McKinley E T, Bugaj J E, Zhao P, et al. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clinical Cancer Research, 2011, 17(10): 3332-3340.