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 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.|
|Incubation time||72 h|
|Animal models||LISN tumor xenograft model in mice|
|Formulation||25mM tartaric acid|
|Dosages||25mg/kg or 75mg/kg daily for 12 days|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
|Solubility||DMSO ≥84 mg/mL|
Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor.
Mulvihill MJ, et al. Future Med Chem. 2009 Sep;1(6):1153-71. PMID: 21425998.
|Related IGF-1R Products|
NVP-AEW541 is a novel, potent and selective inhibitor of IGF-IR kinase with IC50 value of 0.086.
AG-1024 (Tyrphostin) inhibits IGF-1R autophosphorylation with IC50 of 7 μM, is less potent to IR with IC50 of 57 μM and specifically distinguishes between InsR and IGF-1R (as compared to other tyrphostins).
AXL1717 (picropodophyllin, Picropodophyllotoxin, PPP) is a non-competitive, potent, and specific inhibitor of IGF-1Rα/β with IC50 of 1 nM.
BMS-754807 is an ATP-competitive dual-kinase inhibitor of IGF-1R and IR with IC50s of 1.8 nM and 1.7 nM, respectively.
PQ401 is an insulin growth factor-1 receptor (IGF-1R) inhibitor.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.