Sotrastaurin (AEB071)

Catalog No.S2791 Batch:S279103

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Technical Data

Formula

C25H22N6O2
Molecular Weight 438.48 CAS No. 425637-18-9
Solubility (25°C)* In vitro DMSO 88 mg/mL (200.69 mM)
Ethanol 9 mg/mL (20.52 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Sotrastaurin (AEB071) is a potent and selective pan-PKC inhibitor, mostly for PKCθ with Ki of 0.22 nM in a cell-free assay; inactive to PKCζ. Phase 2.
Targets
PKCθ [1]
(Cell-free assay)		 PKCβ1 [1]
(Cell-free assay)		 PKCα [1]
(Cell-free assay)		 PKCη [1]
(Cell-free assay)		 PKCδ [1]
(Cell-free assay)		 View More
0.22 nM(Ki) 0.64 nM(Ki) 0.95 nM(Ki) 1.8 nM(Ki) 2.1 nM(Ki)
In vitro

Sotrastaurin (< 10μM) treatment effectively abrogated at low nanomolar concentration markers of early T-cell activation, such as interleukin-2 secretion and CD25 expression, in primary human and mouse T cells. Sotrastaurin (200 nM) inhibits the CD3/CD28 antibody- and alloantigen-induced T-cell proliferation responses in the absence of nonspecific antiproliferative effects. Sotrastaurin (<3 μM) markedly inhibits lymphocyte function-associated antigen-1-mediated T-cell adhesion. [1]

Sotrastaurin(< 20 μM) selectively impair the proliferation of CD79 mutant ABC DLBCL cell lines, correlating with decreased NF-κB signaling avctivity. AEB071 at concentration of 5 μM induces G1 arrest and/or cell death in CD79 mutant cells. [2]
In vivo

Sotrastaurin (80 mg/kg) results in significant inhibition of in vivo tumor growth in a subcutaneous TMD8 xenograft model in SCID. [2]

Sotrastaurin orally administrated at 10 mg/kg and 30 mg/kg b.i.d. show a dose-dependent immunosuppressive effect leading to pronounced prolongation of heart allograft survival in rats. [3]
Features Unlike former PKC inhibitors, Sotrastaurin does not enhance apoptosis of murine T-cell blasts in a model of activation-induced cell death.

Protocol (from reference)

Kinase Assay:

[1]
  • Protein Kinase Assays

    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.
Cell Assay:

[4]
  • Cell lines

    UM cell lines

  • Concentrations

    5 μM

  • Incubation Time

    24 h

  • Method

    Cells were treated with indicated concentration of drug for 24 h.
Animal Study:

[3]
  • Animal Models

    male Wistar/F rats

  • Dosages

    10 mg/kg and 30 mg/kg

  • Administration

    Orally administrated

References

  • https://pubmed.ncbi.nlm.nih.gov/19491325/
  • https://pubmed.ncbi.nlm.nih.gov/21324920/
  • https://pubmed.ncbi.nlm.nih.gov/20003043/
  • https://pubmed.ncbi.nlm.nih.gov/35352024/

Customer Product Validation

Lysates from H3122 and MGH006 cells treated with 1 µM PMA in the presence or absence of 0.3 µM sotrastaurin (SOT) were fractionated. Immunoblotting was performed with the indicated antibodies.

Data from [ , , Cancer Cell, 2015, 27(3): 397-408 ]

J-Lat A2 cells were stimulated by TPA (10 nM) for 24 h in the presence of the indicated concentrations of AUY922 and sotrastaurin, alone or in combination. Samples were analyzed by FACS and data plotted using MacSynergy II software. (A) Representative McSynergy II plot: areas of the graph above zero indicate an additive or synergistic effect. (B) Representative checkerboard grid used to calculate the plot shown in A.

Data from [ , , Proc Natl Acad Sci USA, 2014, 111(15): E1528-37 ]

Primary mantle cell lymphoma (MCL) cells respond differentially to sotrastaurin and ibrutinib. Primary MCL cells (MCL01-MCL04) were treated with 3 μmol/l sotrastaurin or 400 nmol/l ibrutinib for 2 h (A) or 22 h (B) followed by a stimulation with 3 μg/ml anti-human IgM antibody for 10 min. Subsequently whole cell lysates were analysed by Western blotting. DMSO, dimethyl sulphoxide.

Data from [ , , Br J Haematol, 2016, 173(3):394-403 ]

Western blotting analysis of FLT3ePIM-1 signaling in MV4-11 cells treated with increasing concentrations of SGI-1776, quizartinib, or sotrastaurin for 24 h.

Data from [ , , Biochem Biophys Res Commun, 2018, 10.1016/j.bbrc.2018.07.049 ]

Selleck's Sotrastaurin (AEB071) has been cited by 92 publications

Regulation of Rho guanine nucleotide exchange factor 3 by phosphorylation in the PH domain [ iScience, 2025, 28(6):112753] PubMed: 40546952
Combination of Cbl-b inhibitor NX-1607 and CDK4/6 inhibitor abemaciclib enhances anti-tumor immunity through PLCγ1/ERK-mediated T cell activation [ Cell Signal, 2025, 135:112051] PubMed: 40774352
RalB uncoupling from exocyst is required for endothelial Weibel-Palade body exocytosis [ Mol Biol Cell, 2025, 36(5):ar62] PubMed: 40172988
PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity [ Sci Adv, 2025, 11(36):eadw2568] PubMed: 40911684
Translational genetics identifies a phosphorylation switch in CARD9 required for innate inflammatory responses [ Cell Rep, 2024, 43(3):113944] PubMed: 38489265
Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response [ Cell Rep, 2024, 43(3):113929] PubMed: 38457343
Adaptor protein 3BP2 regulates gene expression in addition to the ubiquitination and proteolytic activity of MALT1 in dectin-1-stimulated cells [ J Biol Chem, 2024, 300(12):107980] PubMed: 39542253
Downregulation of PIK3IP1/TrIP on T cells is controlled by TCR signal strength, PKC, and metalloprotease-mediated cleavage [ J Biol Chem, 2024, 300(12):107930] PubMed: 39454954
RalB uncoupled exocyst mediates endothelial Weibel-Palade body exocytosis [ bioRxiv, 2024, 2024.09.16.613344] PubMed: 39345530
High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101244] PubMed: 37858338

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SHIPPING AND STORAGE
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