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OSI-027

Cat. No. M2099
OSI-027 Structure
Size Price Availability Quantity
5mg USD 90 In stock
10mg USD 175 In stock
50mg USD 480 In stock
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Quality Control
Biological Activity

OSI-027 is a potent, orally bioavailable mammalian target of rapamycin (mTOR) kinase inhibitor with potential antineoplastic activity. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 potently inhibits proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. In contrast to rapamycin, OSI-027 induced apoptosis in a variety of lymphoid cell lines and clinical samples, including specimens of B-cell acute lymphocytic leukemia (ALL), mantle cell lymphoma, marginal zone lymphoma and Sezary syndrome. Furthermore, OSI-027 shows superior efficacy compared with rapamycin in COLO 205 and GEO colon cancer xenograft models. OSI-027 is currently in phase I clinical trials in cancer patients.

Protocol
Cell Experiment
Cell lines MDA-MB-231, MDA MB 435, PC-3, OVCAR-3, A549, DU145, NCI-H2122, U 87 MG and ACHN cell lines
Preparation method For assays of cell proliferation, cells were seeded into 96-well plates and incubated for 3 days in the presence of OSI-027 or OXA-01 at various concentrations. Inhibition of cell growth was determined by luminescent quantification of intracellular ATP content using CellTiterGlo® (Promega). Proliferation on Day 0 vs. 72h was used to plot dose-response curves for IC50 calculations and to determine cell death.
Concentrations 0.1~1μM
Incubation time 72 h
Animal Experiment
Animal models nu/nu CD-1 mice bearing MDA-MB-231 xenograft model
Formulation 20% Trappsol
Dosages 25 or 65 mg/kg QD for 14 days
Administration orally
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 406.44
Formula C21H22N6O3
CAS Number 936890-98-1
Purity 99.07%
Solubility DMSO
Storage at -20°C
References

Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma-dependent apoptosis in lymphoid malignancies.
Gupta M, et al. Blood. 2012 Jan 12;119(2):476-87. PMID: 22080480.

Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.
Bhagwat SV, et al. Mol Cancer Ther. 2011 Aug;10(8):1394-406. PMID: 21673091.

Dual mTORC2/mTORC1 targeting results in potent suppressive effects on acute myeloid leukemia (AML) progenitors.
Altman JK, et al. Clin Cancer Res. 2011 Jul 1;17(13):4378-88. PMID: 21415215.

Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors.
Falcon BL, et al. Cancer Res. 2011 Mar 1;71(5):1573-83. PMID: 21363918.

Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells.
Carayol N, et al. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12469-74. PMID: 20616057.

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Keywords: OSI-027 supplier, mTOR, inhibitors

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