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| 5mg |
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| 25mg |
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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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| Additional Infomation |
Sotrastaurin is a member of the class of maleimides that is maleimide which is substituted at position 3 by an indol-3-yl group and at position 4 by a quinazolin-4-yl group, which in turn is substituted at position 2 by a 4-methylpiperazin-1-yl group. It is a potent and selective inhibitor of protein kinase C and has been investigated as an immunosuppresant in renal transplant patients. It has a role as an EC 2.7.11.13 (protein kinase C) inhibitor, an immunosuppressive agent and an anticoronaviral agent. It is a N-alkylpiperazine, a N-arylpiperazine, a member of indoles, a member of quinazolines and a member of maleimides.
Sotrastaurin has been used in trials studying the basic science and treatment of Uveal Melanoma, Richter Syndrome, Prolymphocytic Leukemia, Recurrent Mantle Cell Lymphoma, and Recurrent Small Lymphocytic Lymphoma, among others. Sotrastaurin is an orally available pan-protein kinase C (PKC) inhibitor with potential immunosuppressive and antineoplastic activities. Sotrastaurin inhibits both T- and B-cell activations via PKC theta and beta isozymes, respectively. Both PKCs are important in the activation of nuclear factor-kappaB (NF-kB). 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. PKC, a family of serine/threonine protein kinases overexpressed in certain types of cancer cells, is involved in cell differentiation, mitogenesis, inflammation, and the activation and survival of lymphocytes. |
| Molecular Formula |
C25H22N6O2
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| Molecular Weight |
438.48
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| Exact Mass |
438.18
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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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| PubChem CID |
10296883
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| Appearance |
Solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.737
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| LogP |
2.56
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
33
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| Complexity |
822
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OAVGBZOFDPFGPJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H22N6O2/c1-30-10-12-31(13-11-30)25-27-19-9-5-3-7-16(19)22(28-25)21-20(23(32)29-24(21)33)17-14-26-18-8-4-2-6-15(17)18/h2-9,14,26H,10-13H2,1H3,(H,29,32,33)
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| Chemical Name |
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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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) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.70 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.70 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2% DMSO +30%PEG 300 +ddH2O: 10 mg/mL |
| 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.
Study of AEB071 (a Protein Kinase C Inhibitor) in Patients With CD79-mutant Diffuse Large B-Cell Lymphoma
CTID: NCT01402440
Phase: Phase 1 Status: Terminated
Date: 2020-12-19
Products are for research use only; We do not sell to patients
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