| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary targets of Sotrastaurin are the PKC isozymes, particularly PKCθ (Ki = 0.22 nM) and PKCβ (Ki = 0.64 nM). It also inhibits PKCα (0.95 nM), PKCη (1.8 nM), PKCδ (2.1 nM), and PKCε (3.2 nM). By inhibiting PKCθ, it blocks T-cell receptor-mediated NF-κB activation and IL-2 production. PKCβ inhibition suppresses B-cell activation. Sotrastaurin also inhibits GSK-3β (IC50 = 229 and 172 nM for α and β isoforms), modulating β-catenin signaling.
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|---|---|
| ln Vitro |
In vitro, Sotrastaurin inhibits PKCθ with a Ki of 0.22 nM and blocks T-cell activation with IC50 values in the low nanomolar range. It suppresses anti-CD3/anti-CD28-induced IL-2 production and CD25 expression in primary human T-cells. In B-cells, it inhibits anti-IgM-induced proliferation. Sotrastaurin also shows antiproliferative activity against various cancer cell lines. The compound is active in the sub-nanomolar to low nanomolar range and is soluble in DMSO.
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| ln Vivo |
In vivo, Sotrastaurin demonstrates immunosuppressive activity in animal models of organ transplantation, reducing graft rejection and prolonging graft survival. It is orally bioavailable and shows dose-dependent inhibition of T-cell and B-cell responses. In preclinical models of autoimmune diseases (psoriasis, uveitis), it reduces inflammation and disease severity. Clinical trials in psoriasis and uveitis showed clinical activity but development was discontinued.
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| Enzyme Assay |
The PKC kinase assay uses recombinant PKC isozymes incubated with a substrate peptide, lipid activators (phosphatidylserine/diacylglycerol), and [γ-³²P]ATP in kinase buffer (20 mM Tris-HCl pH 7.4, 0.1% BSA). Sotrastaurin is added at serial dilutions. The reaction is incubated at 30°C for 10-30 minutes. Phosphorylated substrate is captured on filters and radioactivity quantified by scintillation counting. Ki values are calculated.
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| Cell Assay |
For cell-based assays, primary human T-cells or Jurkat cells are treated with Sotrastaurin. T-cell activation is assessed by measuring IL-2 production (ELISA), CD25 expression (flow cytometry), and NF-κB activation (luciferase reporter). In B-cells, proliferation is measured by [³H]thymidine incorporation. PKC substrate phosphorylation is assessed by Western blot. Cell viability is evaluated using MTT or CellTiter-Glo.
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| Animal Protocol |
In vivo studies with Sotrastaurin employ rodent models of organ transplantation (e.g., heart or skin allograft) or autoimmune disease. The compound is formulated in a suitable vehicle and administered orally by gavage at doses determined from pharmacokinetic studies. Key readouts include graft survival, T-cell infiltration, cytokine levels, and disease severity scores. In autoimmune models, inflammation and tissue damage are assessed histologically.
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| References |
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| Additional Infomation |
Sotrastaurin acetate is the acetate form of sorastatin, an orally administered ubiquitin kinase C (PKC) inhibitor with potential immunosuppressive and antitumor activities. Sotrastaurin inhibits the activation of T cells and B cells through PKC θ and β isoenzymes, respectively. Both PKC isoenzymes play important roles in the activation of nuclear factor κB (NF-κB). Inhibition of PKC β in B cells blocks NF-κB-mediated signaling and downregulates the expression of NF-κB target genes. This may ultimately lead to G1 phase cell cycle arrest and apoptosis in susceptible tumor cells. This drug may have synergistic effects with other chemotherapeutic agents. Protein kinase C (PKC) is a serine/threonine protein kinase that is overexpressed in certain types of cancer cells and participates in cell differentiation, mitosis, inflammation, and lymphocyte activation and survival.
Drug Indications Prevention of kidney transplant rejection Treatment of chronic plaque psoriasis |
| Molecular Formula |
C25H22N6O2.C2H4O2
|
|---|---|
| Molecular Weight |
498.53314
|
| Exact Mass |
498.202
|
| CAS # |
908351-31-5
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| Related CAS # |
908351-31-5 (acetate);425637-18-9;
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| PubChem CID |
24779745
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.799
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
37
|
| Complexity |
853
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1CCN(C2=NC3=CC=CC=C3C(C4=C(C(NC4=O)=O)C5=CNC6=CC=CC=C56)=N2)CC1.CC(O)=O
|
| InChi Key |
RVEUYBMXVVDLFO-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H22N6O2.C2H4O2/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;1-2(3)4/h2-9,14,26H,10-13H2,1H3,(H,29,32,33);1H3,(H,3,4)
|
| Chemical Name |
acetic acid;3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0059 mL | 10.0295 mL | 20.0590 mL | |
| 5 mM | 0.4012 mL | 2.0059 mL | 4.0118 mL | |
| 10 mM | 0.2006 mL | 1.0029 mL | 2.0059 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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