Sotrastaurin (AEB071)
Sotrastaurin (AEB071; CAS 425637-18-9) is a small-molecule inhibitor targeting protein kinase C (PKC), with inhibitory activity against classical and novel PKC isoforms. PKC plays an integral role in immune cell signaling, influencing T-cell activation, proliferation, and cytokine synthesis. Sotrastaurin blocks PKC-mediated pathways, thereby suppressing T-cell activation, proliferation, IL-2 mRNA expression, and NK-cell function, as demonstrated in ex vivo lymphocyte assays. Due to its immunoregulatory properties, Sotrastaurin has potential therapeutic applications in autoimmune conditions, including psoriasis.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 438.48 |
Cas No. | 425637-18-9 |
Formula | C25H22N6O2 |
Synonyms | AEB 071;AEB-071 |
Solubility | ≥21.9 mg/mL in DMSO; insoluble in H2O; ≥2.55 mg/mL in EtOH with ultrasonic |
Chemical Name | 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione |
SDF | Download SDF |
Canonical SMILES | CN1CCN(CC1)C2=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65 |
Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
General tips | We do not recommend long-term storage for the solution, please use it up soon. |
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. |
Description | Sotrastaurin is a potent and selective small-molecule inhibitor of protein kinase C (PKC) with Ki value of 0.22 nM for PKCθ. | |||||
Targets | PKCθ | |||||
IC50 | 0.22 nM |
Quality Control & MSDS
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Chemical structure
