1. Epigenetics
    TGF-beta/Smad
  2. PKC
  3. Sotrastaurin

Sotrastaurin (Synonyms: AEB071)

目录号: HY-10343 纯度: 99.89%
产品使用指南

Sotrastaurin (AEB071) 是一种口服有效的 pan-PKC 抑制剂,作用于 PKCθ,PKCβ,PKCα,PKCη,PKCδ 和 PKCε,Ki 分别为 0.22 nM,0.64 nM,0.95 nM,1.8 nM,2.1 nM 和 3.2 nM。

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Sotrastaurin Chemical Structure

Sotrastaurin Chemical Structure

CAS No. : 425637-18-9

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Top Publications Citing Use of Products

    Sotrastaurin purchased from MCE. Usage Cited in: Cancer Res. 2015 Nov 1;75(21):4538-47.

    AEB071 downregulates APOBEC3B in multiple cancer cell lines. The histogram reports APOBEC3B mRNA levels normalized to the vehicle treated control for each line. The dotted line represents a 50% decrease of APOBEC3B expression due to AEB071. The corresponding immunoblots show APOBEC3B and TUBULIN levels. Each line is treated with AEB071 (10 μM) or vehicle control for 48 hours prior to mRNA and protein analysis.

    Sotrastaurin purchased from MCE. Usage Cited in: Patent. US20180185302A1.

    Representative PKC inhibitor treated cancer cell line experiment. Each line is treated with AEB071 (10 μM) or vehicle control for 48 hours prior to analysis. The histogram reports APOBEC3B mRNA levels normalized to the vehicle treated control for each line.

    Sotrastaurin purchased from MCE. Usage Cited in: Mol Ther Oncolytics. 2018 Aug 29;11:1-13.

    Levels of murine APOBEC3 are measured by ELISA (left panel) and western blot (right panel) from B16 cells infected with VSV-GFP at an MOI of 0.01 at 0, 48, or 96 hr after treatment with a control IgG, a polyclonal anti-IFN-β antibody, or AEB071 (10 μM).
    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    Sotrastaurin (AEB071) is a potent and orally-active pan-PKC inhibitor, with Kis of 0.22 nM, 0.64 nM, 0.95 nM, 1.8 nM, 2.1 nM and 3.2 nM for PKCθ, PKCβ, PKCα, PKCη, PKCδ and PKCε, respectively[1].

    IC50 & Target

    PKCθ

    0.22 nM (Ki)

    PKCβI

    0.64 nM (Ki)

    PKCα

    0.95 nM (Ki)

    PKCη

    1.8 nM (Ki)

    PKCδ

    2.1 nM (Ki)

    PKCε

    3.2 nM (Ki)

    体外研究
    (In Vitro)

    In cell-free kinase assays Sotrastaurin (AEB071) inhibits PKC, with Ki values in the subnanomolar to low nanomolar range. When Sotrastaurin is tested on a selected panel of kinases, the only enzyme on which Sotrastaurin displays an IC50value below 1 μM is glycogen synthase kinase 3β[1]. Sotrastaurin (AEB071) inhibits p-MARCKS, a PKC substrate, and pS6 in all the cell lines, independently of the mutational status. There is a slight inhibition of pERK at lower doses also in the GNA11 mutant cells, but not in the WT cells at any concentrations. This is consistent with previous reports indicating that Sotrastaurin inhibits ERK1/2 phosphorylation in GNAQ mutant cell lines[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    体内研究
    (In Vivo)

    The combination therapy results in a significantly enhanced reduction in tumor volume when compared to either Sotrastaurin (AEB071) or BYL719 alone (p=0.049 vs. BYL719 and p=0.022 vs. Sotrastaurin at day 26). There is even a greater effect when compared to vehicle control (p=0.016)[2]. Sotrastaurin (STN) treatment of liver donors and orthotopic liver transplantation (OLT) recipients (Gr.I) or of OLT recipients alone (Gr.II) prolongs animal survival, as 9 out of 10 rats in Gr. I, and 6 out of 6 rats in Gr.II survive >14 days. In contrast, only 4 out of 10 control OLT recipients remain alive at day 14 (p<0.01)[3].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    分子量

    438.48

    Formula

    C25H22N6O2

    CAS 号
    运输条件

    Room temperature in continental US; may vary elsewhere.

    储存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 6 months
    -20°C 1 month
    溶解性数据
    In Vitro: 

    DMSO : ≥ 50 mg/mL (114.03 mM)

    * "≥" means soluble, but saturation unknown.

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 2.2806 mL 11.4030 mL 22.8061 mL
    5 mM 0.4561 mL 2.2806 mL 4.5612 mL
    10 mM 0.2281 mL 1.1403 mL 2.2806 mL
    *

    请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
    储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

    In Vivo:

    请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

    ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
    分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

    • 1.

      请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (5.70 mM); Clear solution

      此方案可获得 ≥ 2.5 mg/mL (5.70 mM,饱和度未知) 的澄清溶液。

      以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

      将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液
    • 2.

      请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (5.70 mM); Clear solution

      此方案可获得 ≥ 2.5 mg/mL (5.70 mM,饱和度未知) 的澄清溶液。

      以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

      将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
    *以上所有助溶剂都可在 MCE 网站选购。
    参考文献
    Kinase Assay
    [1]

    Classical and novel PKC isotypes are assayed by scintillation proximity assay technology. In brief, the assay is performed in 20 mM Tris-HCl buffer, pH 7.4, and 0.1% bovine serum albumin by incubating 1.5 μM of the peptide substrate with 10 μM [33P]ATP, 10 mM Mg (NO3)2, 0.2 mM CaCl2, and PKC at a protein concentration varying from 25 to 400 ng/mL, and lipid vesicles containing 30 mol% phosphatidylserine, 5 mol% diacylglycerol (DAG), and 65 mol% phosphatidylcholine at a final lipid concentration of 0.5 μM. Incubation is performed for 60 min at room temperature. The reaction is stopped by adding 50 μL of a mixture containing 100 mM EDTA, 200 μM ATP, 0.1% Triton X-100, and 0.375 μg/well streptavidin-coated scintillation proximity assay beads in PBS without Ca2+ and Mg2+. Incorporated radioactivity is measured in a MicroBetaTrilux counter for 1 min. PKCζ is assayed. In situ Thr-219 autophosphorylation status analysis of PKCθ is done by a phospho-site-specific antibody[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    Cells are plated in a 96-well plate and treated with Sotrastaurin, BYL719 or DMSO at indicated concentrations for a period of 5 days. Viability is assessed using Cell Counting Kit. The Combination Index values are calculated using the CompuSyn software. Briefly explained, the plots generated by the CompuSyn software demonstrate the Y-axis combination index values, where CI<1, =1, and >1 indicate synergism, additive effect, and antagonism, respectively. The X-Axis represents the fractional activity, which reflects the fraction of cells inhibited by the treatments relative to vehicle control. For combination index studies, the concentrations tested included Sotrastaurin (0, 125, 250, 500, 1000 nM) and BYL719 (0, 250, 500, 1000, 2000 nM)[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2][3]

    Mice[2]
    6-8 week nu/nu SCID female mice bearing subcutaneously injected 92.1 tumors (7 mice/group) of 100mm3 diameter are treated with vehicle, Sotrastaurin (80mg/kg/d) TID and or BYL719 orally (50mg/kg/d) QD as single agents and in combination, 5 days/week for 2 weeks. After 2 weeks, two animals from each group are sacrificed and tumors are collected to analyze for Western blot. For Omm1 xenogratfs, 6-8 weeks athymic female mice bearing subcutaneously injected Omm1 tumors (7 mice/group) of 100 mm3 diameter are treated with vehicle, Sotrastaurin (80mg/kg/d) TID and or BYL719 orally (50mg/kg/d) QD as single agents and in combination, 5 days/week for 3 weeks. Tumors are homogenized with grinding resins kits. Tumors are collected to analyze for H&E, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Tumors are measured every 2 to 3 days with calipers, and tumor volumes are calculated. Toxicity is monitored by weight loss.
    Rats[3]
    Male Sprague-Dawley (SD) rats (230-250g) are used throughout.Livers from SD rats are stored at 4C in UW solution for 30h, and then transplanted to SD rats with revascularization. Sotrastaurin (30mg/kg b.i.d. via oral gavage) is used in two treatment protocols. In Gr. I (n=10), liver Sotrastaurin is given to liver donors (90min prior to organ harvest) and OLT recipients (90min prior to the transplant, and for three days post-OLT). In Gr. II (n=6), Sotrastaurin is administered to OLT recipients only (according to Gr. I protocol). Gr. III controls are treated with PBS (n=10). OLT survival is assessed at day 14. Separate cohorts in Gr. I (n=3-4/gr) are sacrificed at 6h and 24h; OLT and peripheral blood samples are collected for analyses.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    参考文献
    • 摩尔计算器

    • 稀释计算器

    The molarity calculator equation

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    质量   浓度   体积   分子量 *
    = × ×

    The dilution calculator equation

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    浓度 (start) × 体积 (start) = 浓度 (final) × 体积 (final)
    × = ×
    C1   V1   C2   V2

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    目录号:
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