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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Sotrastaurin (also known as AEB-071; AEB071; AEB 071) is an orally bioavailable, potent and selective pan-PKC inhibitor with potential antineoplastic activity. It inhibits mostly PKCθ with a Ki of 0.22 nM in a cell-free assay and has no effects against PKCζ. Sotrastaurin inhibits both T- and B-cell activations via PKC theta and beta isozymes, respectively. Inhibition of PKC beta in B-cells results in prevention of NF-kB-mediated signaling and down regulation of NF-kB target genes. This may eventually lead to an induction of G1 cell cycle arrest and tumor cell apoptosis in susceptible tumor cells. This agent may act synergistically with other chemotherapeutic agents.
| ln Vitro |
In a cell-free kinase test, sotrastaurin (AEB071) inhibits PKC with Ki values in the subnanomolar to low nanomolar range. Glycogen synthase kinase 3β was the sole enzyme for which sotrastaurin displayed an IC50 value < 1 μM when tested on a chosen panel of kinases[1]. Regardless of the presence of mutations, sotrastaurin (AEB071) suppresses p-MARCKS, a substrate of PKC, and pS6 in all cell lines. In GNA11 mutant cells, there was also a small suppression of pERK at lower levels, but not at any concentration in WT cells. This is in accordance with other studies that shown how sotrastaurin prevents ERK1/2 phosphorylation in cell lines with GNAQ mutations [2].
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| ln Vivo |
When compared to Sotrastaurin (AEB071) or BYL719 alone, combination therapy significantly reduced the tumor volume (p=0.049 vs. BYL719, p=0.022 vs. Sotrastaurin, day 26). In comparison to control controls, the effect was much more pronounced (p=0.016)[2]. Animal survival was prolonged by sotrastaurin (STN) therapy of liver donors, orthotopic liver transplantation (OLT) recipients (Gr. I) or OLT recipients alone (Gr. II). Just nine out of ten rats. In groups I and II, six out of six rats lived longer than fourteen days. On the other hand, at day 14, only 4 out of 10 control OLT patients remained alive (p<0.01) [3].
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| References |
[1]. Evenou JP, et al. The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation. J Pharmacol Exp Ther. 2009 Sep;330(3):792-801.
[2]. Musi E, et al. The phosphoinositide 3-kinase α selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells. Mol Cancer Ther. 2014 May;13(5):1044-53 [3]. Kamo N, et al. Sotrastaurin, a protein kinase C inhibitor, ameliorates ischemia and reperfusion injury in rat orthotopic liver transplantation. Am J Transplant. 2011 Nov;11(11):2499-507 |
| Molecular Formula |
C25H22N6O2
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| Molecular Weight |
438.48
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| CAS # |
425637-18-9
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| Related CAS # |
908351-31-5 (acetate);425637-18-9;
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| SMILES |
O=C(C(C1=C2C=CC=CC2=NC(N3CCN(C)CC3)=N1)=C4C5=CNC6=C5C=CC=C6)NC4=O
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2806 mL | 11.4030 mL | 22.8061 mL | |
| 5 mM | 0.4561 mL | 2.2806 mL | 4.5612 mL | |
| 10 mM | 0.2281 mL | 1.1403 mL | 2.2806 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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