Name: Sotrastaurin (AEB071)
Brand: Selleck Chemicals
SKU: S2791
Rating: 5 (84 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.97%

99.97

Gerelateerde doelwitten	TGF-beta/Smad ROCK Bcr-Abl
Overig PKC Inhibitoren	Darovasertib (LXS196) PMA chemical (Phorbol 12-myristate 13-acetate) Enzastaurin Go 6983 Bisindolylmaleimide I (GF109203X) Go 6976 Bisindolylmaleimide IX (Ro 31-8220) Mesylate Ruboxistaurin (LY333531) Hydrochloride Rottlerin PKC-theta inhibitor

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
T cell	Function Assay	100 nM	3 h	DMSO	inhibits rRNA synthesis	25691158
HUVECs	Function Assay	500nM	1 h		Reduces DTX-Triggered Endothelial Dysfunction	25634538
A549	Function Assay	0.1 μM	24 h		decreases the relative PKC-α level on cell membrane cotreated 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	Growth Inhibition Assay	0.1 μM	24 h		enhances growth inhibition cotreated with AS-IV	25218161
Mel202	Growth Inhibition Assay	0.5 μM	3 h	DMSO	enhances IR-induced reduction in cell viability	24595385
92.1	Growth Inhibition Assay	0.5 μM	3 h	DMSO	enhances IR-induced reduction in cell viability	24595385
OCM3	Growth Inhibition Assay	0.5 μM	3 h	DMSO	enhances IR-induced reduction in cell viability	24595385
Mel202	Growth Inhibition Assay	0.5 μM	3 h	DMSO	increases IR-induced cell cycle arrest	24595385
92.1	Growth Inhibition Assay	0.5 μM	3 h	DMSO	increases IR-induced cell cycle arrest	24595385
OCM3	Growth Inhibition Assay	0.5 μM	3 h	DMSO	increases IR-induced cell cycle arrest	24595385
Jeko-1	Growth Inhibition Assay	0-4 μM		DMSO	inhibits cell growth dose dependently	24362935
Mino	Growth Inhibition Assay	0-4 μM		DMSO	inhibits cell growth dose dependently	24362935
Rec-1	Growth Inhibition Assay	0-4 μM		DMSO	inhibits cell growth dose dependently	24362935
SP49	Growth Inhibition Assay	0-4 μM		DMSO	inhibits cell growth dose dependently	24362935
Jeko-1	Function Assay	2.5 μM	12 h	DMSO	downregulates NF-κB target genes	24362935
Mino	Function Assay	2.5 μM	12 h	DMSO	downregulates NF-κB target genes	24362935
Rec-1	Function Assay	2.5 μM	12 h	DMSO	downregulates NF-κB target genes	24362935
SP49	Function Assay	2.5 μM	12 h	DMSO	downregulates NF-κB target genes	24362935
CD3+ T	Function Assay	0-500 nM	1 h		inhibits NF-κB phosphorylation in a dose dependent manner	23573283
Mel202	Growth Inhibition Assay	0-5 μM	72 h	DMSO	inhibits cell growth dose dependently	22653968
Omm1.3	Growth Inhibition Assay	0-5 μM	72 h	DMSO	inhibits cell growth dose dependently	22653968
92.1	Growth Inhibition Assay	0-5 μM	72 h	DMSO	inhibits cell growth dose dependently	22653968
Mel202	Growth Inhibition Assay	5 μM	24 h	DMSO	induces G1 arrest	22653968
Omm1.3	Growth Inhibition Assay	5 μM	24 h	DMSO	induces G1 arrest	22653968
92.1	Growth Inhibition Assay	5 μM	24 h	DMSO	induces G1 arrest	22653968
Mel202	Apoptosis Assay	5 μM	72 h	DMSO	induces apoptosis slightly	22653968
Omm1.3	Apoptosis Assay	5 μM	72 h	DMSO	induces apoptosis	22653968
92.1	Apoptosis Assay	5 μM	72 h	DMSO	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
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
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
B-cells	Function assay				Inhibition of PKCbeta in mouse B cells assessed as reduction in IgM-stimulated cell proliferation, IC50 = 0.234 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
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Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	438.48	Formule	C₂₅H₂₂N₆O₂	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	425637-18-9	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	CN1CCN(CC1)C2=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 87 mg/mL (198.41 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 40 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken	Unlike former PKC inhibitors, Sotrastaurin does not enhance apoptosis of murine T-cell blasts in a model of activation-induced cell death.
Targets/IC₅₀/Ki	PKCθ (Cell-free assay) 0.22 nM(Ki) PKCβ1 (Cell-free assay) 0.64 nM(Ki) PKCα (Cell-free assay) 0.95 nM(Ki) PKCη (Cell-free assay) 1.8 nM(Ki) PKCδ (Cell-free assay) 2.1 nM(Ki) PKCε (Cell-free assay) 3.2 nM(Ki)
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. 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.
Kinase Assay	Eiwitkinase-assays
Kinase Assay	Sotrastaurin (AEB071) werd getest op klassieke en nieuwe PKC-isotypes met behulp van scintillatie nabijheidsassay-technologie. Kortom, de assay wordt uitgevoerd in 20 mM Tris-HCl-buffer, pH 7.4, en 0.1% runderserumalbumine door 1.5 μM van het peptidesubstraat te incuberen met 10 μM [³³P]ATP, 10 mM Mg (NO3)₂, 0.2 mM CaCl₂, en PKC bij een eiwitconcentratie variërend van 25 tot 400 ng/mL, en lipid vesicles die 30 mol% fosfatidylserine, 5 mol% diacylglycerol (DAG), en 65 mol% fosfatidylcholine bevatten bij een uiteindelijke lipideconcentratie van 0.5 μM. Incubatie wordt gedurende 60 min bij kamertemperatuur uitgevoerd. De reactie wordt gestopt door toevoeging van 50 μl van een mengsel dat 100 mM EDTA, 200 μM ATP, 0.1% Triton X-100, en 0.375 μg/well streptavidine-gecoate scintillatie nabijheidsassay-korrels in PBS zonder Ca²⁺ en Mg²⁺ bevat. Geïncorporeerde radioactiviteit wordt gedurende 1 min gemeten in een MicroBetaTrilux-teller.
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. 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.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/19491325/ [2] https://pubmed.ncbi.nlm.nih.gov/21324920/ [3] https://pubmed.ncbi.nlm.nih.gov/20003043/ [4] https://pubmed.ncbi.nlm.nih.gov/35352024/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	p-Marcks / p-ERK / p-AKT / p-S6 / Marcks / ERK / AKT / S6 PKCα / PKCδ / PKCβ / PKCε / PKCθ Bcl-xl / XIAP / Survivin Cyclin D1 / p27(Kip1) pPKCδ/θ / phosphorylated MARCKS / p53 / MDM2 / PUMA / p21		22653968
Growth inhibition assay	Cell viability		22653968

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
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

Veelgestelde vragen (Frequently Asked Questions)

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

Antwoord:
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.

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Sotrastaurin (AEB071) PKC Remmer

Molecuulgewicht: 438.48

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie over klinische proeven (Clinical Trial Information)

Veelgestelde vragen (Frequently Asked Questions)

Sotrastaurin (AEB071) PKC Remmer

Molecuulgewicht: 438.48

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie over klinische proeven (Clinical Trial Information)

Veelgestelde vragen (Frequently Asked Questions)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)