OSI-027

Catalog No.S2624 Synonyms: ASP4786

OSI-027 Chemical Structure

Molecular Weight(MW): 406.44

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

Size Price Stock Quantity  
In DMSO USD 200 In stock
USD 120 In stock
USD 210 In stock
USD 570 In stock
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5 Customer Reviews

  • Cells were treated during 7 days with OSI-027 (C, D). Response is expressed as the percentage of vehicle-treated control (±s.e.m.). Control is normalised at 100%.

    Br J Cancer, 2016, 114(6):650-8. OSI-027 purchased from Selleck.

    H460 and A549 cells were treated with 20 μM OSI-027 for the indicated amount of time. Protein levels were estimated using western blot analysis. The blot shown is representative of 3 independent experiments

    Sci Rep, 2016, 6:28945. OSI-027 purchased from Selleck.

  • HCC cell lines (HepG2 and SMMC-7721) or the primary human HCC cells (“HCC-1/-2”) were treated with AT406 (at applied concentrations) or plus OSI-027 (“OSI”, 100 nM), cells were further cultured for indicated periods of time, the caspase-3 activity (A, for HepG2 cells) was tested; Cell apoptosis was tested by the ssDNA ELISA assay (B, F–H) or the TUNEL staining assay (C, for HepG2 cells). HepG2 cells were pretreated with the caspase-3 specific inhibitor z-DEVD-fmk (50 μM) or the general caspase inhibitor z-VAD-fmk (50 μM) for 1 hour, followed by AT406 (10 μM) plus OSI-027 (100 nM) combination treatment (“Both”), cells were further cultured and subjected to ssDNA ELISA assay of apoptosis (D) and MTT assay of cell viability (E). “Veh” stands for 0.2% of DMSO (D and E). *indicated statistically significant differences as compared to “Ctrl” group. #indicated statistically significant differences as compared to “AT406” only group (A–C, F–H). ##indicated statistically significant differences as compared to “Both” group (D and E).

    Oncotarget, 2017, 8(6):9466-9475. OSI-027 purchased from Selleck.

    EdU staining of GBC-SD cells treated with OSI-027 (6.25 μM) and/or 5-FU (6.25 μg/mL) was performed by using Click-iT EdU Imaging Kit. The percentages of EdU-positive cells have been provided in the right panel.

    Eur Rev Med Pharmacol Sci, 2016, 20(9):1699-706.. OSI-027 purchased from Selleck.

  • Urol Oncol 2013 1078-1439(13)00251-2. OSI-027 purchased from Selleck.

Purity & Quality Control

Choose Selective mTOR Inhibitors

Biological Activity

Description OSI-027 is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM in cell-free assays, and more than 100-fold selectivity observed for mTOR than PI3Kα, PI3Kβ, PI3Kγ or DNA-PK. Phase 1.
Targets
mTOR [4]
(Cell-free assay)
mTORC1 [1]
(Cell-free assay)
mTORC2 [1]
(Cell-free assay)
PI3Kγ [4]
(Cell-free assay)
4 nM 22 nM 65 nM 0.42 μM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human SQ20B cells MlvDR5l1d3SxeHnjbZR6KGG|c3H5 NWHvR3hvPzJiaB?= NIW5ZmlEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUWTJyQjDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVEvOyEQvF2= MnHPNlQ1PDV|MUG=
human Caki1 cells MXXDfZRwfG:6aXPpeJkh[XO|YYm= M3HhV|czKGh? M{\LSWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGNic2lzIHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9NU46KM7:TR?= M4POb|I1PDR3M{Gx
human SKHEP1 cells Ml76R5l1d3SxeHnjbZR6KGG|c3H5 M{nBR|czKGh? Mn\CR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2tJTVBzIHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9N{4zKM7:TR?= MUmyOFQ1PTNzMR?=
human DU145 cells NUPXcnFJS3m2b4TvfIlkcXS7IHHzd4F6 NF;mdXM4OiCq NHzDV|lEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBFXTF2NTDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVQvOSEQvF2= NUX3OnR7OjR2NEWzNVE>
human HCT116 cells NVzxS4lsS3m2b4TvfIlkcXS7IHHzd4F6 MkP2O|IhcA>? NHvSVHNEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJS1RzMU[gZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF02NjZizszN MXeyOFQ1PTNzMR?=
human ColoR cells MXvDfZRwfG:6aXPpeJkh[XO|YYm= MWG3NkBp M4nyfWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGNwdG:UIHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9OU45KM7:TR?= NF\VWXczPDR2NUOxNS=>
human COLO205 cells M3j1SGN6fG:2b4jpZ4l1gSCjc4PhfS=> NHzVS4g4OiCq M{C0SmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGNQVE9{MEWgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF02NjhizszN NWj3SpI4OjR2NEWzNVE>
human OVCAR3 cells Mlq1R5l1d3SxeHnjbZR6KGG|c3H5 M17QbFczKGh? MU\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDPWmNCWjNiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3ME24MlEh|ryP NXzuTVFIOjR2NEWzNVE>
human HOP62 cells M2rQSWN6fG:2b4jpZ4l1gSCjc4PhfS=> NGPuelk4OiCq NHqwdHdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJV1B4MjDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVQyKM7:TR?= M4HLXlI1PDR3M{Gx
human COLO205 cells MV7DfZRwfG:6aXPpeJkh[XO|YYm= M1n5PVczKGh? NIS4XoZEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBEV0yRMkC1JINmdGy|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[Xl? MXKyOFg{PjB5MB?=
human HOP62 cells Mn3PR5l1d3SxeHnjbZR6KGG|c3H5 MWi3NkBp NGDZeFBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJV1B4MjDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6 MmHuNlQ5OzZyN{C=

... Click to View More Cell Line Experimental Data

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]

Protocol

Kinase Assay:

[1]

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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:

[2]

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  • Cell lines: U937, KG-1, KBM-3B, ML-1, HL-60, and MEG-01
  • Concentrations: 0-10 μM
  • Incubation Time: 72 hours
  • Method:

    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)
Animal Research:

[1]

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  • Animal Models: GEO colorectal cells are injected s.c. into the right flank of nu/nu CD-1 mice.
  • Formulation: Dissolved in DMSO and then diluted in water.
  • Dosages: ≤65 mg/kg
  • Administration: Administered via gavage.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 18 mg/mL (44.28 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
1% DMSO+30% polyethylene glycol+1% Tween 80
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 406.44
Formula

C21H22N6O3

CAS No. 936890-98-1
Storage powder
Synonyms ASP4786

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00698243 Completed Any Solid Tumor or Lymphoma Astellas Pharma Inc June 2008 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID