| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Midostaurin targets a broad range of protein kinases, including PKCalpha/beta/gamma, Syk, Flk-1 (VEGFR2), Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRbeta, and VEGFR1/2. By competitively binding to the ATP-binding pocket of these kinases, it inhibits their ability to phosphorylate downstream substrates, thereby disrupting key signaling pathways involved in cell proliferation and survival.
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| ln Vitro |
Midostaurin-d5 is used to study the potent, multi-targeted protein kinase inhibitory activity of its non-deuterated form, Midostaurin. Midostaurin inhibits the activity of PKCalpha/beta/gamma, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRbeta, and VEGFR1/2 with IC₅0 values ranging from 22-500 nM, demonstrating its broad-spectrum activity against both serine/threonine and tyrosine kinases. It also induces apoptosis, cell cycle arrest, and inhibits angiogenesis in vitro.
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| ln Vivo |
As a labeled version of an approved drug, the in vivo activity of Midostaurin-d5 is equivalent to that of unlabeled Midostaurin. Midostaurin is the active pharmaceutical ingredient in Rydapt, which is approved for the treatment of acute myeloid leukemia (AML) with a FLT3 mutation.
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| Enzyme Assay |
A standard kinase inhibition assay, such as a radiometric or time-resolved fluorescence (TR-FRET) assay, is used to determine IC₅0 values. For a specific kinase like PKCalpha, the enzyme is incubated with its substrate (e.g., a biotinylated peptide), ATP, and varying concentrations of Midostaurin-d5. The reaction is then terminated, and phosphorylated product is quantified by adding a detection mix (e.g., an antibody specific for the phosphorylated peptide) and measuring the signal.
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| Cell Assay |
Cells (e.g., MV4-11 AML cells with FLT3-ITD mutation) are seeded in microplates and treated with a dose titration of Midostaurin-d5. After incubation (e.g., 72 hours), the inhibition of cell growth is assessed using an MTT or CellTiter-Glo viability assay. For specific pathway analysis, treated cells are lysed, and the lysates are analyzed by Western blotting with phospho-specific antibodies (e.g., p-FLT3, p-STAT5, p-ERK) to confirm target inhibition.
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| Animal Protocol |
For in vivo evaluation, standard protocols involve administering Midostaurin-d5 to tumor-bearing xenograft mouse models via oral gavage, as it is an orally bioavailable drug. The compound can be administered daily at doses that would be determined by prior MTD studies. Blood samples are collected at various time points post-dose for PK analysis using Midostaurin-d5 itself as the internal standard for LC-MS/MS. Plasma samples are pre-treated using a protein precipitation method with methanol containing Midostaurin-D5 as an internal standard.
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| ADME/Pharmacokinetics |
Midostaurin-d5 is primarily intended for use as an internal standard for the quantification of Midostaurin by GC- or LC-MS. The pharmacokinetics of Midostaurin include extensive hepatic metabolism, primarily by the CYP3A4 isoenzyme, and it has a high oral bioavailability and a long terminal half-life of approximately 20 hours.
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| Toxicity/Toxicokinetics |
Midostaurin-d5 is not intended for therapeutic use; its toxicity is not assessed directly for this reagent. The active drug, Midostaurin, has been studied extensively in clinical trials. Common adverse reactions in AML patients include febrile neutropenia, nausea, vomiting, and headache.
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| References | |
| Additional Infomation |
Midostaurin-d5 is a research-grade isotopically labeled standard. Its non-deuterated parent drug, Midostaurin (Rydapt), is a prescription medicine approved by the FDA for the treatment of newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive, in combination with chemotherapy, and for the treatment of advanced systemic mastocytosis (ASM), and mast cell leukemia (MCL).
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| Molecular Formula |
C35H25D5N4O4
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|---|---|
| Related CAS # |
Midostaurin;120685-11-2
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| Appearance |
Typically exists as solid at room temperature
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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.) |
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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