Application of OSI-906
A technology of OSI-906, 1. OSI-906, applied in the application field of OSI-906, can solve the problem of thyroid eye disease and the like that there is no IGF-1R small molecule inhibitor
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Embodiment 1
[0034] Example 1 Inhibitory effect of OSI-906 on IGF-1R
[0035] The overexpression and activation of IGF-1R can promote the proliferation of tumor cells, and the IC of the compound on the inhibition of cell proliferation can be detected by adding different concentrations of the compound 50 result. OSI-906 was diluted to different final concentrations and co-cultured with human breast cancer cells MCF-7 in 96-well plates for 3 days, the serum concentration was 10%, and the growth inhibition of cells was detected by CellTiterGlo instrument. The IC of OSI-906 was obtained by calculating and fitting the corresponding relationship between different concentrations of OSI-906 and the number of cells (calculated by the measured fluorescence intensity of extracellular ATP). 50 The value is 177nM.
Embodiment 2
[0036] Example 2 The efficacy of OSI-906 in animal models of hyperthyroidism
[0037]Rat models of hyperthyroidism and thyroid-related eye disease were induced by intraperitoneal injection of bovine thyroglobulin, and the effect of OSI-906 on rat thyroid-related eye disease was observed, including the following steps:
[0038] (1) Adult healthy male SD rats were selected and randomly divided into 3 groups, ten rats in each group, which were normal control group, model-making control group and model-making administration group. Rats in the model group were injected with bovine thyroglobulin intraperitoneally at a dose of 150 μg / rat every 2 weeks to establish the model, and the model was completed for 4 weeks. The specific dosage regimen is operated according to Table 1:
[0039] Table 1
[0040]
[0041] (2) Animals were euthanized 4 weeks after administration and samples were collected. After the rats were euthanized, the extraocular muscles were collected, stained, and ...
Embodiment 3
[0045] Example 3 The efficacy of OSI-906 in animal models of polycystic ovary syndrome
[0046] The model of polycystic ovary syndrome was established by subcutaneous injection of dihydrotestosterone in SD female rats, and the evaluation of OSI-906 in the model was selected by monitoring the changes in rat weight gain, the number of atresic follicles, and the changes in epithelial cells in vaginal smears. The efficacy of the drug, specifically including the following steps:
[0047] (1) Select adult healthy female SD rats with similar days of birth and body fat, and divide them into 3 groups randomly, ten rats in each group, which are normal control group, modeling control group and modeling administration group respectively. After grouping, each There was no significant difference in the body weight of rats in the two groups. Rats in the model group were raised under the same conditions, and the rats in the model group were subcutaneously injected with dihydrotestosterone at...
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