Sotrastaurin (AEB071)

製品コードS2791 バッチS279101

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H22N6O2
分子量 438.48 CAS No. 425637-18-9
Solubility (25°C)* 体外 DMSO 87 mg/mL (198.41 mM)
Ethanol 2 mg/mL (4.56 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
in vitro

Treatment with Sotrastaurin (AEB071) at concentrations below 10 μM effectively abrogated markers of early T-cell activation—such as interleukin-2 secretion and CD25 expression—in primary human and mouse T cells at low nanomolar levels. At 200 nM, it inhibits CD3/CD28 antibody- and alloantigen-induced T-cell proliferation without nonspecific antiproliferative effects. Furthermore, this compound (<3 μM) markedly impairs lymphocyte function-associated antigen-1-mediated T-cell adhesion.[1]

At concentrations under 20 μM, it selectively impairs the proliferation of CD79 mutant ABC DLBCL cell lines, correlating with reduced NF-κB signaling activity. A concentration of 5 μM induces G1 arrest and/or cell death in CD79 mutant cells.[2]
in vivo

In a subcutaneous TMD8 xenograft model in SCID mice, Sotrastaurin (AEB071) (80 mg/kg) results in significant inhibition of in vivo tumor growth. [2]

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

プロトコル(参考用のみ)

キナーゼアッセイ Protein Kinase Assays
Sotrastaurin (AEB071) was assayed for classical and novel PKC isotypes using 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.
細胞アッセイ 細胞株 UM cell lines
濃度 5 μM
反応時間 24 h
実験の流れ Cells were treated with the indicated concentration of Sotrastaurin (AEB071) for 24 h.
動物実験 動物モデル male Wistar/F rats
投薬量 10 mg/kg and 30 mg/kg
投与方法 Orally administrated

参考

  • 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/

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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