Linsitinib (Synonyms: OSI 906; OSI-906; OSI906) |
| Catalog No.GC15749 |
IGF1R/IR inhibitor,potent and novel
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 867160-71-2
Sample solution is provided at 25 µL, 10mM.
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Linsitinib (OSI-906) is a potent and novel small-molecule inhibitor inhibiting insulin receptor (IR) and IGF-1 receptor (IGF-1R) kinases with IC50 value of 75nM and 35nM, respectively1.
Studies in 3T3/hulGF-1R(LISN) cells showed that linsitinib inhibits the ligant-dependent autophosphorylation of IGF-1R and its downstream signaling pathways including pERK1/2, pAKT, p-p70S6K. Linsitinib showed anti-proliferative effects in different cancer cell lines including colorectal cells (SW620), breast tumor cells (DY4475) and mouse fibroblast cells (3T3/hulGF-1R) with EC50 of 21nM, 86nM, and 78nM, respectively1.
Linsitinib administrated orally in LISN derived xenograft model has been shown to suppress the tumor growth in a dose-dependent manner 1.
References:
1. Mulvihill MJ1, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y, Arnold LD, Gibson NW, Ji QS. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009 Sep;1(6):1153-71
| Cell experiment: [1] | |
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Cell lines |
HepG2, Hep3B, Huh-7, PLC/PRF/5, SNU-387 and SNU-423 cells |
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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. |
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Reaction Conditions |
3 μM, 20 hours |
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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 experiment: [2] | |
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Animal models |
Female athymic nude mice injected with NCI-H292 or NCI-H441 cells |
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Dosage form |
Oral administration, 60 mg/kg |
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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. |
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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. |
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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. | |
| Cas No. | 867160-71-2 | SDF | |
| Synonyms | OSI 906; OSI-906; OSI906 | ||
| Chemical Name | 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol | ||
| Canonical SMILES | CC1(CC(C1)C2=NC(=C3N2C=CN=C3N)C4=CC5=C(C=C4)C=CC(=N5)C6=CC=CC=C6)O | ||
| Formula | C26H23N5O | M.Wt | 421.51 |
| Solubility | ≥ 21.1mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3724 mL | 11.8621 mL | 23.7242 mL |
| 5 mM | 0.4745 mL | 2.3724 mL | 4.7448 mL |
| 10 mM | 0.2372 mL | 1.1862 mL | 2.3724 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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