OSI-027

製品コードS2624 別名:ASP4786

OSI-027化学構造

分子量(MW):406.44

OSI-027は一種の選択性的で、有効な二重mTORC1とmTORC2抑制剤で、無細胞試験でIC50値が22 nM と65 nMに分かれて、mTORに作用する選択性はPI3Kα、PI3Kβ、PI3Kγ或いは DNA-PKに作用する選択性より100倍余りが高くなります。臨床1期。

サイズ 価格(税別) 在庫  
JPY 33200.00 あり
JPY 19920.00 あり
JPY 34860.00 あり
JPY 94620.00 あり

カスタマーフィードバック(5)

  • 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.

製品安全説明書

mTOR阻害剤の選択性比較

生物活性

製品説明 OSI-027は一種の選択性的で、有効な二重mTORC1とmTORC2抑制剤で、無細胞試験でIC50値が22 nM と65 nMに分かれて、mTORに作用する選択性はPI3Kα、PI3Kβ、PI3Kγ或いは DNA-PKに作用する選択性より100倍余りが高くなります。臨床1期。
ターゲット
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
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human SQ20B cells NVrmOppUS3m2b4TvfIlkcXS7IHHzd4F6 MmqwO|IhcA>? MYTDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTVVIxSiClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBKSzVyPUGuN{DPxE1? MWKyOFQ1PTNzMR?=
human Caki1 cells MVrDfZRwfG:6aXPpeJkh[XO|YYm= NGfsbmQ4OiCq MVrDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDDZYtqOSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBKSzVyPUGuPUDPxE1? M2nnT|I1PDR3M{Gx
human SKHEP1 cells NVrJb25kS3m2b4TvfIlkcXS7IHHzd4F6 M4C4UVczKGh? NHHHUlREgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUU0iHUEGgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0{NjJizszN NUmxU4NWOjR2NEWzNVE>
human DU145 cells MXLDfZRwfG:6aXPpeJkh[XO|YYm= MU[3NkBp M4LmeWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGRWOTR3IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9OE4yKM7:TR?= MmqwNlQ1PDV|MUG=
human HCT116 cells M37SRWN6fG:2b4jpZ4l1gSCjc4PhfS=> M1jvVVczKGh? MnuzR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTGNVOTF4IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9OU43KM7:TR?= NELNZo4zPDR2NUOxNS=>
human ColoR cells MmXUR5l1d3SxeHnjbZR6KGG|c3H5 NGP6[GE4OiCq NYTZcJlmS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hS2:ub2KgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF02NjhizszN NG\yTXMzPDR2NUOxNS=>
human COLO205 cells MXPDfZRwfG:6aXPpeJkh[XO|YYm= NYO3T4YxPzJiaB?= M37pe2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGNQVE9{MEWgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF02NjhizszN NVvBN|J6OjR2NEWzNVE>
human OVCAR3 cells MULDfZRwfG:6aXPpeJkh[XO|YYm= MWK3NkBp MkXrR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gU3ZESVJ|IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9PE4yKM7:TR?= NIe5cYYzPDR2NUOxNS=>
human HOP62 cells MWjDfZRwfG:6aXPpeJkh[XO|YYm= NEi0XWo4OiCq MYjDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIU3A3OiClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBKSzVyPUSxJO69VQ>? MkPjNlQ1PDV|MUG=
human COLO205 cells NXHOcG9oS3m2b4TvfIlkcXS7IHHzd4F6 NIHUXoE4OiCq MULDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDDU2xQOjB3IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZk> MnzZNlQ5OzZyN{C=
human HOP62 cells MkLtR5l1d3SxeHnjbZR6KGG|c3H5 M{T6OFczKGh? MW\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIU3A3OiClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5 NHuzNYYzPDh|NkC3NC=>

多くの細胞株試験データを見る場合、クリックしてください

体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

+ 展開

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.
細胞試験:

[2]

+ 展開
  • 細胞株: U937, KG-1, KBM-3B, ML-1, HL-60, and MEG-01
  • 濃度: 0-10 μM
  • 反応時間: 72 hours
  • 実験の流れ:

    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.


    (参考用のみ)
動物試験:

[1]

+ 展開
  • 動物モデル: GEO colorectal cells are injected s.c. into the right flank of nu/nu CD-1 mice.
  • 製剤: Dissolved in DMSO and then diluted in water.
  • 投薬量: ≤65 mg/kg
  • 投与方法: Administered via gavage.
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 18 mg/mL (44.28 mM)
Water Insoluble
Ethanol Insoluble
体内 順序で溶剤を入れること:
1% DMSO+30% polyethylene glycol+1% Tween 80
30 mg/mL

* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 406.44
化学式

C21H22N6O3

CAS No. 936890-98-1
保管
別名 ASP4786

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

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

技術サポート

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

mTOR信号経路図

mTOR Inhibitors with Unique Features

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID