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OSI-930

Cat. No. M1805
OSI-930 Structure
Size Price Availability Quantity
10mg USD 170 In stock
50mg USD 560 In stock
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Quality Control
Biological Activity

OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase insert domain receptor (KDR), which is currently being evaluated in clinical studies. OSI-930 selectively inhibits Kit and KDR with similar potency in intact cells and also inhibits these targets in vivo following oral dosing. We have investigated the relationships between the potency observed in cell-based assays in vitro, the plasma exposure levels achieved following oral dosing, the time course of target inhibition in vivo, and antitumor activity of OSI-930 in tumor xenograft models. In the mutant Kit-expressing HMC-1 xenograft model, prolonged inhibition of Kit was achieved at oral doses between 10 and 50 mg/kg and this dose range was associated with antitumor activity. Similarly, prolonged inhibition of wild-type Kit in the NCI-H526 xenograft model was observed at oral doses of 100 to 200 mg/kg, which was the dose level associated with significant antitumor activity in this model as well as in the majority of other xenograft models tested. The data suggest that antitumor activity of OSI-930 in mouse xenograft models is observed at dose levels that maintain a significant level of inhibition of the molecular targets of OSI-930 for a prolonged period. Furthermore, pharmacokinetic evaluation of the plasma exposure levels of OSI-930 at these effective dose levels provides an estimate of the target plasma concentrations that may be required to achieve prolonged inhibition of Kit and KDR in humans and which would therefore be expected to yield a therapeutic benefit in future clinical evaluations of OSI-930.

Protocol
Cell Experiment
Cell lines HMC-1 cell line
Preparation method For assays of cell proliferation, cells were seeded into 96-well plates and incubated for 2 to 3 days in the presence of OSI-930 at various concentrations. Inhibition of cell growth was determined by luminescent quantitation of the intracellular ATP content using CellTiterGlo (Promega, Madison, WI).
Concentrations 0~100nM
Incubation time 2-3 days
Animal Experiment
Animal models HMC-1 tumor xenograft model
Formulation either Labrafil M 1944 CS (Gattefossé) or polyethylene glycol (PEG)-400/water (50:50)] at an appropriate concentration to deliver the desired dose at 20 mL/kg
Dosages a single oral dose of 5, 10, 25, or 50 mg/kg
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
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 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.

Chemical Information
Molecular Weight 443.44
Formula C22H16F3N3O2S
CAS Number 728033-96-3
Purity 100.00%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Acta Haematol (2014). Figure 2. OSI-930
Method ELISA-based assay
Cell Lines NCI-H526 cells, HUVECs and NIH-3T3 cells
Concentrations 100 nmol/L
Incubation Time 2 to 3 h
Results The concentration of OSI-930 that induced these phenotypic effects was comparable to that required to inhibit Kit phosphorylation in the HMC-1 cell line under the same culture conditions
Rating
References

OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models.
Garton AJ, et al. Cancer Res. 2006 Jan 15;66(2):1015-24. PMID: 16424037.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: OSI-930 supplier, VEGFR/PDGFR, inhibitors

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