OSI-906 (Linsitinib) is an orally small-molecule inhibitor of IGF-1R with potential antineoplastic activity. IGF-1R has been viewed as an important therapeutic target due to its involvement in the growth and proliferation in a variety of human cancers, including adrenocortical carcinoma (ACC), ovarian and non-small cell lung cancers. A major challenge in the development of IGF-1R inhibitors is to avoid blocking the closely related insulin receptor that regulates glucose levels in the blood. OSI-906 (Linsitinib) selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Overexpressed in a variety of human cancers, IGFR-1 stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis. OSI-906 slowed the growth of IGF-1R-dependent tumors, and it also reduced proliferation and/or survival of a broad panel of tumor cell lines.
Cell Experiment | |
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Cell lines | NSCLC(H292, H358 and H1703) and CRC(Colo205, HT-29 and RKO) tumor cell lines |
Preparation method | Cell proliferation assay. cells were seeded into 96-well plates in appropriate media containing FCS 10% and incubated for 3 days in the presence of OSI-906 at various concentrations. Inhibition of cell growth was determined by luminescent quantitation of intracellular ATP content using CellTiterGlo (Promega, Madision , WI, USA). Data were presented as a fraction of maximal proliferation, caculated by dividing the cellular density in the presence of varying concentrations of OSI-906 by the cellular density of control cells treated with vehicle (DMSO) only. |
Concentrations | 0~10 μM |
Incubation time | 72 h |
Animal Experiment | |
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Animal models | LISN tumor xenograft model in mice |
Formulation | 25mM tartaric acid |
Dosages | 25mg/kg or 75mg/kg daily for 12 days |
Administration | orally |
Molecular Weight | 421.49 |
Formula | C26H23N5O |
CAS Number | 867160-71-2 |
Solubility (25°C) | DMSO 62 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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