Inicio>>Signaling Pathways>> TGF-β / Smad Signaling>> PKC>>Sotrastaurin (AEB071)

Sotrastaurin (AEB071) (Synonyms: AEB 071;AEB-071)

Catalog No.GC15520

Sotrastaurin (AEB071) (AEB071) es un inhibidor PAN-PKC potente y oralmente activo, con KIS de 0.22 nm, 0.64 nm, 0.95 nm, 1.8 nm, 2.1 nm y 3.2 nm para PKC&&&&&&&&&&&&&&&&77TRES. offlineefficient_models_2022q2.md;, PKCδen_es_2021q4.mdand PKCε, respectively.en_es_2021q4.md

Products are for research use only. Not for human use. We do not sell to patients.

Sotrastaurin (AEB071) Chemical Structure

Cas No.: 425637-18-9

Tamaño Precio Disponibilidad Cantidad
10mM (in 1mL DMSO)
95,00 $
Disponible
5mg
85,00 $
Disponible
10mg
137,00 $
Disponible
25mg
357,00 $
Disponible
50mg
588,00 $
Disponible

Tel:(909) 407-4943 Email: sales@glpbio.com

Reseñas de cliente

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product has been cited by 2 publications

Product Documents

Quality Control & SDS

View current batch:

Protocol

Kinase experiment [1]:

Binding assays

Classical and novel PKC isotypes were assayed by scintillation proximity assay technology. In brief, the assay was 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 was performed for 60 min at room temperature. The reaction was 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 was measured in a MicroBetaTrilux counter for 1 min.

Cell experiment [2]:

Cell lines

GNAQ/GNA11-mutant Uveal Melanoma cell lines

Preparation method

The solubility of this compound in DMSO is >21.9 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

125, 250, 500, 1000 nM; 5 days

Applications

AEB071 inhibited cell proliferation in GNAQ/GNA11-mutant Uveal Melanoma cell lines with inhibition of the PKC/ERK1/2 pathway.

Animal experiment [2]:

Animal models

nu/nu SCID female mice bearing GNAQ mutant xenograft

Dosage form

Oral administration, 80mg/kg/d, three times daily

Application

AEB071/BYL719 combination inhibited in vivo tumor growth in a GNAQ mutant xenograft model.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Evenou J P, Wagner J, Zenke G, et al. The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation[J]. Journal of Pharmacology and Experimental Therapeutics, 2009, 330(3): 792-801.

[2]. Musi E, Ambrosini G, De Stanchina E, et al. The phosphoinositide 3-kinase α selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells[J]. Molecular cancer therapeutics, 2014, 13(5): 1044-1053.

Background

AEB071 is an inhibitor of protein kinase C (PKC). The PKC inhibitor which can block the T-cell activation has the ability of immune suppression [1].

The protein kinase C (PKC) isoforms is very important in cell signaling, proliferation, differentiation, migration, survival, and death. PKC family has many isoforms. Among the PKC isoforms, PKC isoforms have basal effect on the T cells’ activation and other immune cell functions [2,3].

ABE071 is a potent inhibitor of novel and classical PKC isoforms. Through the inhibition of PKC, AEB071 can depress the activation and proliferation of T-cell and decrease the production of cytokine.ABE071 can also suppress the NK cell activity. Ex vivo stimulation of lymphocytes from subjects exposed to single doses of AEB071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and IL2 mRNA expression

AEB071 is an effective treatment strategy for the cure of autoimmune diseases. According to the Psoriasis Area Severity Index (PASI) score, after 2 weeks’ treatment with 300 mg bid AEB071, Clinical severity of psoriasis was reduced up to 69% compared with baseline[2,3].

References:
[1].  Weckbecker G1, Pally C, Beerli C, et al. Effects of the novel protein kinase C inhibitor AEB071 (Sotrastaurin) on rat cardiac allograft survival using single agent treatment or combination therapy with cyclosporine, everolimus or FTY720. Transpl Int. 2010 May 1;23(5):543-52
[2].  Skvara H1, Dawid M, Kleyn E, Wolff B, et al. The PKC inhibitor AEB071 may be a therapeutic option for psoriasis. J Clin Invest. 2008 Sep;118(9):3151-9.
[3].   Matz M1, Weber U, Mashreghi MF, et al. Effects of the new immunosuppressive agent AEB071 on human immune cells. Nephrol Dial Transplant. 2010 Jul;25(7):2159-67

Chemical Properties

Cas No. 425637-18-9 SDF
Sinónimos AEB 071;AEB-071
Chemical Name 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione
Canonical SMILES CN1CCN(CC1)C2=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65
Formula C25H22N6O2 M.Wt 438.48
Solubility ≥ 21.9mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.2806 mL 11.403 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
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reseñas

Review for Sotrastaurin (AEB071)

Average Rating: 5 ★★★★★ (Based on Reviews and 23 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for Sotrastaurin (AEB071)

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.