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OSI-027

Catalog No. T6319 CAS 936890-98-1

Synonyms: ASP4786, OSI027

OSI-027 (ASP4786) is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, and more than 100-fold selectivity observed for mTOR than PI3Kα, PI3Kβ, PI3Kγ or DNA-PK. Phase 1.

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OSI-027, CAS 936890-98-1

Pack Size	Availability	Price/USD
1 mg	In stock	$ 35.00
2 mg	In stock	$ 48.00
5 mg	In stock	$ 78.00
10 mg	In stock	$ 141.00
25 mg	In stock	$ 261.00
50 mg	In stock	$ 409.00
100 mg	In stock	$ 596.00
1 mL * 10 mM (in DMSO)	In stock	$ 81.00

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Purity: 98%

Biological Description

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Description	OSI-027 (ASP4786) is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, and more than 100-fold selectivity observed for mTOR than PI3Kα, PI3Kβ, PI3Kγ or DNA-PK. Phase 1.
Targets&IC50	mTORC1:22 nM, mTORC2:65 nM
In vitro	OSI-027 shows the selective and ATP competitive inhibition activities against mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively. In addition, OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC50 of 1 μM in cell-based assays. [1] OSI-027 exhibits anti-proliferative activities against several acute leukemia cell lines of myeloid/megakaryocytic origin in a dose-dependent manner, including U937, KG-1, KBM-3B, ML-1, HL-60, and MEG-01 cells. [2] A recent study shows that inhibition of mTORC1/2 by OSI-027 effectively suppresses phosphorylation of Akt (S473) and cell proliferation in breast cancer cells. [3]
In vivo	In GEO colorectal xenograft, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors, including 4E-BP1, Akt, and S6 phosphorylation. Furthermore, mTORC1 and mTORC2 inhibition together by OSI-027 potently inhibits tumor growth more than mTORC1 inhibition by rapamycin. [1]
Kinase Assay	Biochemical assays: mTORC1 and mTORC2 inhibition is assayed using native enzyme complex immunoprecipitated from HeLa lysates at 1 mM ATP. To prepare whole cell lysates from HeLa cells, 25 g cell pellet is lysed in 60 mL of ice-cold buffer A [40 mM HEPES (pH 7.5), 120 mM NaCl, 1 mM EDTA, 10 mM sodium pyrophosphate, 10 mM glycerophosphate, 50 mM NaF, 0.5 mM orthovanadate, and EDTA-free protease inhibitors containing 0.3% CHAPS] for 30 minutes on a magnetic stirrer in a cold room. After clearing of the lysates by centrifugation at 13,000 g for 10 minutes, Protein G-coated 384-well plates are incubated with 0.25 μg of mTOR antibody in 15 μL of buffer A for 1 hour at 4 °C. To each well, 40 μg of HeLa cell lysate in 15 μL of buffer A is added and incubated overnight at 4 °C to immunoprecipitate mTOR complexes. Plates are washed 3 times with buffer A and twice with immunoprecipitation wash buffer [Buffer B: 50 mM HEPES (pH 7.5) and 150 mM NaCl]. OSI-027 is added at 10 μM concentration to each well and DMSO is added to the control wells. The reaction is started by adding 150 ng of His-tagged 4E-BP1 as a substrate in the presence or absence of 100 μM ATP to each well in 25 μL of freshly prepared kinase buffer [Buffer C: 20 mM HEPES (pH 7.5), 10 mM MgCl2, 4 mM MnCl2, 10 mM β-mercaptoethanol, and 200 μM vanadate] and incubated at room temperature (RT) for 30 minutes. The reaction is stopped by transferring 25 μL of reaction mixture from each well to corresponding wells of fresh Ni-chelate-coated plates and incubated overnight at 4 °C followed by 2 hours at 37 °C. To detect phosphorylation of 4E-BP1, the plates are washed once with TBST (Tris-buffered saline containing 0.1% Tween-20) containing 5% skim milk powder. To each well, 25 μL of 1:1,000 diluted phospho-4E-BP1 antibodies in TBST containing 5% skim milk are added and incubated for 1 hour at RT.The plates are washed once with TBST and then 25 μL of anti-rabbit HRP (diluted 1:10,000) in TBST containing 5% skim milk is added. The plates are incubated for 1 hour at RT and washed 5 times with TBST. For detection of phospho-4E-BP1, 25 μL of chemiluminescent reagents A+B is added and chemiluminescence is measured using an Analyst plate reader.
Cell Research	Inhibition of proliferation is measured using the Cell Titer Glo Assay , as noted in figure legends. To generate dose–response curves, cell lines are seeded at a density of 5,000 cells per well in a 96-well plate. After 24 hours of plating, cells are dosed with varying concentrations of either OSI-027 or rapamycin. The signal for Cell Titer Glo Assay is determined 72 hours after dosing and normalized to that of vehicle-treated controls. Inhibition of proliferation, relative to vehicle-treated controls, is expressed as a fraction of 1 and graphed using PRISM software. (Only for Reference)

Synonyms	ASP4786, OSI027
Molecular Weight	406.44
Formula	C21H22N6O3
CAS No.	936890-98-1

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 15 mg/mL (36.9 mM)

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

References and Literature

1. Falcon BL, et al. Cancer Res, 2011, 71(5), 1573-1583. 2. Altman JK, et al. Clin Cancer Res, 2011, 17(13), 4378-4388. 3. Li H, et al. Breast Cancer Res Treat, 2012, 134(3), 1057-1066. 4. Bhagwat SV, et al. Mol Cancer Ther. 2011, 10(8), 1394-1406. 6. Zhi X, et al. OSI-027 modulates acute graft-versus-host disease after liver transplantation in a rat model. Liver Transpl. 2017 Sep;23(9):1186-1198.

Citations

1. Sun C Y, Li Y Z, Cao D, et al. Rapamycin and trametinib: a rational combination for treatment of NSCLC. International Journal of Biological Sciences. 2021, 17(12): 3211-3223.

Related compound libraries

This product is contained In the following compound libraries：

Kinase Inhibitor Library Inhibitor Library Anti-Cancer Drug Library Drug Repurposing Compound Library Highly Selective Inhibitor Library Anti-Cancer Active Compound Library Anti-Cancer Clinical Compound Library Glutamine Metabolism Compound Library PI3K-AKT-mTOR Compound Library Anti-Ovarian Cancer Compound Library

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Keywords

OSI-027 936890-98-1 Autophagy DNA Damage/DNA Repair PI3K/Akt/mTOR signaling DNA-PK mTOR PI3K inhibit ASP4786 OSI 027 ASP 4786 Mammalian target of Rapamycin ASP7486 OSI027 ASP-4786 ASP-7486 ASP 7486 Inhibitor inhibitor

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