Enzastaurin (LY317615)

製品コードS1055

Enzastaurin (LY317615)化学構造

分子量(MW):515.61

Enzastaurin (LY317615)は一種の有効なPKCβの選択性阻害剤で、無細胞試験でIC50値が6 nMですが、PKCβに作用する選択性はPKCα、PKCγとPKCεに作用する選択性より6倍-20倍が高くなります。臨床3期。

サイズ 価格(税別) 在庫  
JPY 18094.00 あり
JPY 19920.00 あり
JPY 61420.00 あり
JPY 161020.00 あり

カスタマーフィードバック(4)

  •  

    The protein kinase C (PKC)–specific inhibitor enzastaurin
    induces apoptosis of lupus B cells and prevents lupus development
    in Sle mice. C, Levels of serum IgG anti–double-stranded DNA
    (anti-dsDNA) and antihistone/anti-dsDNA autoantibodies from
    vehicle-treated control mice and enzastaurin-treated mice, as analyzed
    by enzyme-linked immunosorbent assay. Bars in A–C show the mean 
    SD of 3 independent experiments. D, Representative immunofluorescent
    images of IgG deposition (top) and glomeruli (bottom) in kidney
    sections from Sle1.Sle3 mice treated with vehicle or enzastaurin. Original
    magnification  20 (top);  40 (bottom). PAS  periodic acid–Schiff.

    Arthritis Rheum 2013 65, 1022-31. Enzastaurin (LY317615) purchased from Selleck.

     

    The protein kinase C (PKC)–specific inhibitor enzastaurin
    induces apoptosis of lupus B cells and prevents lupus development
    in Sle mice. A, Effect of enzastaurin on apoptosis of lupus B cells.
    Purified splenic B cells were treated with anti-IgM antibody in the
    presence or absence (control) of enzastaurin for 48 hours and analyzed
    with an annexin V detection kit. The fractions of annexin V–positive
    (apoptotic) cells in the samples treated with only anti-IgM (control)
    are set at 1. B, Sensitivity of human 9G4-positive and 9G4-negative
    B cells to PKC inhibition. Purified splenic B cells were treated with
    enzastaurin for 24 hours. The apoptotic fractions from untreated
    samples are set at 1. Results are representative of 2 independent
    experiments.

    Arthritis Rheum 2013 65, 1022-31. Enzastaurin (LY317615) purchased from Selleck.

  • (a and b) Isolated murine splenic B220+ B cells were pretreated with dasatinib (5 μM), a Lyn inhibitor; LY294002 (5 μM), a PI3K inhibitor; ibturinib (1 μM), a BTK inhibitor; enzastaurin (1 μM), a PKC β inhibitor; U0126 (3 μM), an ERK inhibitor; SP600126 (2 μM), a JNK inhibitor or SB20358 (1 μM), a p38 inhibitor for 1 h, followed by stimulation with anti-CD180 antibody (0.2 μg mL−1) or mouse IFN-α (1000 U mL−1) for 4 h. qPCR analysis of the expression of IFIT1 (a) and MX1 (b).

    Cell Mol Immunol, 2017, 14(2):192-202. Enzastaurin (LY317615) purchased from Selleck.

     

    PKC II contributes to the depolarization-induced enhancement of KCNQ currents. C, PKC  inhibitor enzastaurin (2 μM) significantly reduced the depolarization (ND96-K)-induced increase in membrane PKC II levels. D, enzastaurin blocked the depolarization (0 mV)-induced increase of KCNQ2/Q3 current. **, p < 0.01 compared with the control.

     

    J Biol Chem 2011 286, 39760-7. Enzastaurin (LY317615) purchased from Selleck.

製品安全説明書

PKC阻害剤の選択性比較

生物活性

製品説明 Enzastaurin (LY317615)は一種の有効なPKCβの選択性阻害剤で、無細胞試験でIC50値が6 nMですが、PKCβに作用する選択性はPKCα、PKCγとPKCεに作用する選択性より6倍-20倍が高くなります。臨床3期。
ターゲット
PKCβ [1]
(Cell-free assay)
PKCα [1]
(Cell-free assay)
PKCγ [1]
(Cell-free assay)
PKCε [1]
(Cell-free assay)
6 nM 39 nM 83 nM 110 nM
体外試験

Enzastaurin application results in a marked dose-dependent inhibition of growth in all MM cell lines investigated, including MM.1S, MM.1R, RPMI 8226 (RPMI), RPMI-Dox40 (Dox40), NCI-H929, KMS-11, OPM-2, and U266, with IC50 from 0.6-1.6 μM. Enzastaurin direct impacts human tumor cells, inducing apoptosis and suppressing proliferation in cultured tumor cells. Enzastaurin also suppresses the phosphorylation of GSK3βser9, ribosomal protein S6S240/244, and AKTThr308 while having no direct effect on VEGFR phosphorylation. [1] Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. When combined with GSK3 inhibitors, enzastaurin demonstrated an enhancement of cytotoxicity levels. Treatment with a combination of enzastaurin and the GSK3 inhibitor AR-A014418 led to increased levels of β-catenin total protein and β-catenin-mediated transcription. Blocking of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin induced the same cytotoxic effects as that of enzastaurin plus AR-A014418. Additionally, treatment with enzastaurin and AR-A014418 decreased the mRNA levels and surface expression of CD44. [2]

体内試験 Treatment of xenografts with Enzastaurin and radiation produced greater reductions in density of microvessels than either treatment alone. The decrease in microvessel density corresponded to delayed tumor growth. [3]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

+ 展開

Kinase inhibition assays:

The inhibition of PKCβII, PKCα, PKCε, or PKCγ activity by enzastaurin is determined using a filter plate assay format measuring 33P incorporation into myelin basic protein substrate. Reactions are done in 100 μL reaction volumes in 96-well polystyrene plates with final conditions as follows: 90 mM HEPES (pH 7.5), 0.001% Triton X-100, 4% DMSO, 5 mM MgCl2, 100 μM CaCl2, 0.1 mg/mL phosphatidylserine, 5 μg/mL diacetyl glyerol, 30 μM ATP, 0.005 μCi/μL 33ATP, 0.25 mg/mL myelin basic protein, serial dilutions of enzastaurin (1-2,000 nM), and recombinant human PKCβII, PKCα, PKCε, or PKCγ enzymes (390, 169, 719, or 128 pM, respectively). Reactions are started by addition of the enzyme and incubated at room temperature for 60 minutes. They are then quenched with 10% H3PO4, transferred to multiscreen anionic phosphocellulose 96-well filter plates, incubated for 30 to 90 minutes, filtered and washed with 4 volumes of 0.5% H3PO4 on a vacuum manifold. Scintillation cocktail is added and plates are read on a Microbeta scintillation counter. IC50 values are determined by fitting a three-variable logistic equation to the 10-point dose-response data using ActivityBase 4.0.
細胞試験:

[1]

+ 展開
  • 細胞株: HCT116 and U87MG cells
  • 濃度: 0.3-4 μM
  • 反応時間: 72 hours
  • 実験の流れ:

    Induction of apoptosis by enzastaurin is measured by nucleosomal fragmentation and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and staining in HCT116 and U87MG cell lines. Briefly, 5 × 103 cells are plated per well in 96-well plates (1% FBS-supplemented media conditions), incubated with or without Enzastaurin for 48 to 72 hours. The absorbance values are normalized to those from control-treated cells to derive a nucleosomal enrichment factor at all concentrations as per the manufacturer's protocol. The concentrations studied ranges from 0.1 to 10 μM. In situ TUNEL staining is assayed with the In situ Cell Death Detection, Fluorescein kit. Cells (7.5 ?104) are plated per well in 6-well plates and incubated 72 hours in 1% FBS-supplemented media ?Enzastaurin. Fluorescein-labeled DNA strand breaks are detected with the BD epics flow cytometer. Ten thousand, single-cell, FITC-staining events are collected for each test.


    (参考用のみ)
動物試験:[1] [3]
+ 展開
  • 動物モデル: Athymic nude mice; Mouse besring human MM tumors
  • 製剤: 10% acacia in water; dissolved in 100% ethanol and diluted 1:10 in D5W
  • 投薬量: 75 mg/kg twice daily; 30 mg/kg twice daily
  • 投与方法: By gavage
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 30 mg/mL (58.18 mM)
Water Insoluble
Ethanol Insoluble
体内 順序で溶剤を入れること:
15% Captisol
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 515.61
化学式

C32H29N5O2

CAS No. 170364-57-5
保管
別名 N/A

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
NCT00108056 Terminated Glioma National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) April 7, 2005 Phase 1
NCT01432951 Active, not recruiting Solid Tumor|Lymphoma, Malignant Eli Lilly and Company November 2011 Phase 1
NCT01388335 Completed Solid Tumor|Lymphoma, Malignant Eli Lilly and Company August 2011 Phase 1
NCT00685633 Withdrawn Prostate Cancer Eastern Cooperative Oncology Group|National Cancer Institute (NCI) December 2008 Phase 2
NCT00744991 Completed Cutaneous T-Cell Lymphoma Eli Lilly and Company September 2008 Phase 2
NCT00718419 Completed Waldenstroms Macroglobulinemia|Multiple Myeloma Eli Lilly and Company July 2008 Phase 2

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

PKC信号経路図

PKC Inhibitors with Unique Features

相関PKC製品

Tags: Enzastaurin (LY317615)を買う | Enzastaurin (LY317615) ic50 | Enzastaurin (LY317615)供給者 | Enzastaurin (LY317615)を購入する | Enzastaurin (LY317615)費用 | Enzastaurin (LY317615)生産者 | オーダーEnzastaurin (LY317615) | Enzastaurin (LY317615)化学構造 | Enzastaurin (LY317615)分子量 | Enzastaurin (LY317615)代理店
×
細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID