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
* <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.)

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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

Customer Product Validation

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

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

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

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

Selleck's Sotrastaurin (AEB071) has been cited by 84 publications

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
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
Alternative splicing of HDAC7 regulates its interaction with 14-3-3 proteins to alter histone marks and target gene expression [ Cell Rep, 2023, 42(3):112273] PubMed: 36933216
Alternative splicing of HDAC7 regulates its interaction with 14-3-3 proteins to alter histone marks and target gene expression [ Cell Rep, 2023, 42(3):112273] PubMed: 36933216
Trace amine-associated receptor 1 regulation of Kv1.4 channels in trigeminal ganglion neurons contributes to nociceptive behaviors [ J Headache Pain, 2023, 24(1):49] PubMed: 37158881
GATA1 deletion in human pluripotent stem cells increases differentiation yield and maturity of neutrophils [ iScience, 2023, 26(10):107804] PubMed: 37720099
Exercise-acclimated microbiota improves skeletal muscle metabolism via circulating bile acid deconjugation [ iScience, 2023, 26(3):106251] PubMed: 36915683
Exercise-acclimated microbiota improves skeletal muscle metabolism via circulating bile acid deconjugation [ iScience, 2023, 10.1016/j.isci.2023.106251] PubMed: 36915683

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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