Toggle Nav

Linsitinib

In stock
Catalog No.
A8334
IGF1R/IR inhibitor,potent and novel
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$130.00
In stock
Evaluation Sample
$28.00
In stock
5mg
$110.00
In stock
10mg
$190.00
In stock
50mg
$470.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt421.51
Cas No.867160-71-2
FormulaC26H23N5O
SynonymsOSI 906; OSI-906; OSI906
Solubility≥21.1mg/mL in DMSO
Chemical Name3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol
SDFDownload SDF
Canonical SMILESCC1(CC(C1)C2=NC(=C3N2C=CN=C3N)C4=CC5=C(C=C4)C=CC(=N5)C6=CC=CC=C6)O
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment: [1]

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 experiment: [2]

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.

Biological Activity

Description OSI-906 (Linsitinib) is a selective inhibitor of IGF-1R with IC50 of 35 nM; modestly potent to InsR with IC50 of 75 nM.
Targets IGF-1R InsR        
IC50 35 nM 75 nM        

Quality Control

Chemical structure

Linsitinib

Related Biological Data

Linsitinib

Related Biological Data

Linsitinib

Related Biological Data

Linsitinib

Related Biological Data

Linsitinib