Sotrastaurin (AEB071)

製品コード：S2791 純度：99.97%

Sotrastaurin (AEB071) is a potent and selective pan-PKC inhibitor, mostly for PKCθ with K_i of 0.22 nM in a cell-free assay; inactive to PKCζ. Phase 2.

CAS No. 425637-18-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40500	国内在庫あり
5mg	JPY 25500	国内在庫あり
25mg	JPY 100500	国内在庫あり
1g	JPY 598500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

文献中Selleckの製品使用例（83）

製品安全説明書

現在のバッチを見る：純度： 99.97%

99.97

Sotrastaurin (AEB071)関連製品

関連ターゲット	PKCα PKCβ PKCγ PKCδ PKCε PKCζ PKCη PKCθ PKCι	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library	もっと見る

シグナル伝達経路

PKCシグナル伝達経路

PKC阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
92.1	Growth Inhibition Assay	0-5 μM	72 h	inhibits cell growth dose dependently	22653968
Omm1.3	Growth Inhibition Assay	0-5 μM	72 h	inhibits cell growth dose dependently	22653968
Mel202	Growth Inhibition Assay	0-5 μM	72 h	inhibits cell growth dose dependently	22653968
CD3+ T	Function Assay	0-500 nM	1 h	inhibits NF-κB phosphorylation in a dose dependent manner	23573283
SP49	Function Assay	2.5 μM	12 h	downregulates NF-κB target genes	24362935
Rec-1	Function Assay	2.5 μM	12 h	downregulates NF-κB target genes	24362935
Mino	Function Assay	2.5 μM	12 h	downregulates NF-κB target genes	24362935
Jeko-1	Function Assay	2.5 μM	12 h	downregulates NF-κB target genes	24362935
OCM3	Growth Inhibition Assay	0.5 μM	3 h	increases IR-induced cell cycle arrest	24595385
92.1	Growth Inhibition Assay	0.5 μM	3 h	increases IR-induced cell cycle arrest	24595385
Mel202	Growth Inhibition Assay	0.5 μM	3 h	increases IR-induced cell cycle arrest	24595385
OCM3	Growth Inhibition Assay	0.5 μM	3 h	enhances IR-induced reduction in cell viability	24595385
92.1	Growth Inhibition Assay	0.5 μM	3 h	enhances IR-induced reduction in cell viability	24595385
Mel202	Growth Inhibition Assay	0.5 μM	3 h	enhances IR-induced reduction in cell viability	24595385
A549	Growth Inhibition Assay	0.1 μM	24 h	enhances growth inhibition cotreated with AS-IV	25218161
A549	Function Assay	0.1 μM	24 h	reduces the expression levels of MMP-2, MMP-9 and integrin β1	25218161
A549	Function Assay	0.1 μM	24 h	decreases the relative PKC-α level on cell membrane cotreated AS-IV	25218161
HUVECs	Function Assay	500nM	1 h	Reduces DTX-Triggered Endothelial Dysfunction	25634538
T cell	Function Assay	100 nM	3 h	inhibits rRNA synthesis	25691158
Mel202	Growth Inhibition Assay	5 μM	24 h	induces G1 arrest	22653968
Omm1.3	Growth Inhibition Assay	5 μM	24 h	induces G1 arrest	22653968
92.1	Growth Inhibition Assay	5 μM	24 h	induces G1 arrest	22653968
Mel202	Apoptosis Assay	5 μM	72 h	induces apoptosis slightly	22653968
Omm1.3	Apoptosis Assay	5 μM	72 h	induces apoptosis	22653968
92.1	Apoptosis Assay	5 μM	72 h	induces apoptosis signifcantly	22653968
Mel202	Function Assay	5 μM	24 h	inhibits expression and phosphorylation of PKC isoforms	22653968
Omm1.3	Function Assay	5 μM	24 h	inhibits expression and phosphorylation of PKC isoforms	22653968
92.1	Function Assay	5 μM	24 h	inhibits expression and phosphorylation of PKC isoforms	22653968
HBL1	Growth Inhibition Assay	0.16-20 μM	5 d	IC50=0.5 μM	21324920
TMD8	Growth Inhibition Assay	0.16-20 μM	5 d	IC50=0.2 μM	21324920
OCI-Ly10	Growth Inhibition Assay	0.16-20 μM	5 d	IC50=1.3 μM	21324920
U2932	Growth Inhibition Assay	0.16-20 μM	5 d	IC50=10 μM	21324920
OCI-Ly3	Growth Inhibition Assay	0.16-20 μM	5 d	IC50＞20 μM	21324920
SuDHL2	Growth Inhibition Assay	0.16-20 μM	5 d	IC50＞20 μM	21324920
SuDHL4	Growth Inhibition Assay	0.16-20 μM	5 d	IC50＞20 μM	21324920
DB	Growth Inhibition Assay	0.16-20 μM	5 d	IC50＞20 μM	21324920
SP49	Growth Inhibition Assay	0-4 μM		inhibits cell growth dose dependently	24362935
Rec-1	Growth Inhibition Assay	0-4 μM		inhibits cell growth dose dependently	24362935
Mino	Growth Inhibition Assay	0-4 μM		inhibits cell growth dose dependently	24362935
Jeko-1	Growth Inhibition Assay	0-4 μM		inhibits cell growth dose dependently	24362935
Jurkat T	Function assay		5 hrs	Inhibition of PKCtheta in human Jurkat T cells assessed as reduction in anti-CD3/CD28 antibody-induced T-cell activation by measuring decrease in IL-2 secretion after 5 hrs by luciferase reporter gene assay, IC50 = 0.081 μM.	28131714
bone marrow cells	Antiproliferative assay		4 days	Antiproliferative activity against CBA mouse bone marrow cells assessed as inhibition of [3H]thymidine incorporation after 4 days, IC50 = 3.7 μM.	19827831
Jurkat IL-2	Growth Inhibition Assay			IC50=6.71 ± 3.76 μM	19940259
PBMC IL-2	Growth Inhibition Assay			IC50=4.84 ± 1.70 μM	19940259
Jurkat	Function assay			Inhibition of TCR/CD28-mediated human T cell activation in Jurkat cells expressing human IL2 promoter by luciferase reporter gene assay, IC50 = 0.054 μM.	19827831
B-cells	Function assay			Inhibition of PKCbeta in mouse B cells assessed as reduction in IgM-stimulated cell proliferation, IC50 = 0.234 μM.	28131714
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Sotrastaurin (AEB071) is a potent and selective pan-PKC inhibitor, mostly for PKCθ with K_i of 0.22 nM in a cell-free assay; inactive to PKCζ. Phase 2.

特性

Unlike former PKC inhibitors, Sotrastaurin does not enhance apoptosis of murine T-cell blasts in a model of activation-induced cell death.

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)	もっとクリックする
0.22 nM(Ki)	0.64 nM(Ki)	0.95 nM(Ki)	1.8 nM(Ki)	2.1 nM(Ki)	もっとクリックする

In Vitro
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]
Kinase Assay	Protein Kinase Assays
Kinase Assay	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.
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pPKCδ/θ / phosphorylated MARCKS / p53 / MDM2 / PUMA / p21 Cyclin D1 / p27(Kip1) Bcl-xl / XIAP / Survivin PKCα / PKCδ / PKCβ / PKCε / PKCθ p-Marcks / p-ERK / p-AKT / p-S6 / Marcks / ERK / AKT / S6		29593251
	Growth inhibition assay	Cell viability		22653968

In Vivo
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]
動物実験	動物モデル	male Wistar/F rats
	投与量	10 mg/kg and 30 mg/kg
	投与経路	Orally administrated

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT02273219	Completed	Uveal Melanoma	Columbia University	November 19 2014	Phase 1
NCT01801358	Terminated	Uveal Melanoma	Array Biopharma now a wholly owned subsidiary of Pfizer\|Array BioPharma	August 2013	Phase 1\|Phase 2
NCT01430416	Completed	Uveal Melanoma	Novartis Pharmaceuticals\|Novartis	December 20 2011	Phase 1
NCT01402440	Terminated	Diffuse Large B-Cell Lymphoma	Novartis Pharmaceuticals\|Novartis	November 2011	Phase 1

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/ + 展開

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/

+ 展開

化学情報

分子量	438.48	化学式	C₂₅H₂₂N₆O₂
CAS No.	425637-18-9	SDF	Download Sotrastaurin (AEB071) SDFをダウンロードする
Smiles	CN1CCN(CC1)C2=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 87 mg/mL ( (198.41 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 40 mg/mL

Water : Insoluble

モル濃度計算器

in vivo Batch: Add solvents to the product individually and in order.				投与溶液組成計算機
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.
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.
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.

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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よくある質問（FAQ）

質問1:
Could you give me the information about how to prepare it for oral administration in mice?

回答
It can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution which can be used for injection, and in 2% DMSO/corn oil at 10 mg/ml as a suspension for oral administration.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):