| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Idasanutlin-d3-1 targets MDM2 (mouse double minute 2 homolog), a negative regulator of the tumor suppressor protein p53. By binding to MDM2, Idasanutlin prevents the MDM2-p53 interaction, thereby blocking MDM2-mediated ubiquitination and proteasomal degradation of p53. This leads to stabilization and activation of p53, resulting in cell cycle arrest, apoptosis, and anti-tumor activity.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an impact on a drug's pharmacokinetics and metabolic profile, it has drawn attention [1].
Idasanutlin (unlabeled) demonstrates potent inhibition of the MDM2-p53 interaction in cell-free fluorescence polarization (FP) assays. The IC50 for MDM2 binding is in the low nanomolar range. Idasanutlin-d3-1 is not typically used in activity assays but rather as an analytical standard. However, the labeled compound retains the biological activity of the parent molecule, although it is used primarily for quantification purposes. |
| ln Vivo |
In cell-based assays, Idasanutlin-d3-1 is used as a tracer to study cellular uptake and accumulation of the parent drug. The unlabeled Idasanutlin induces p53 stabilization and activation in p53-wild-type cancer cell lines (e.g., SJSA-1, HCT116), leading to upregulation of p21 and MDM2, G1 cell cycle arrest, and apoptosis. The labeled version is used to quantify drug exposure in these cells by LC-MS/MS.
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| Enzyme Assay |
The binding affinity of Idasanutlin to MDM2 is characterized using a cell-free fluorescence polarization (FP) competition assay. A fluorescently labeled p53-derived peptide (e.g., FITC-labeled PMI peptide) is incubated with recombinant MDM2 protein in the presence of varying concentrations of Idasanutlin. The displacement of the labeled peptide is measured by FP. The IC50 is calculated from the dose-response curve. Idasanutlin-d3-1 is not used in this assay.
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| Cell Assay |
To assess cellular activity, p53-wild-type cancer cells (e.g., SJSA-1, HCT116) are treated with Idasanutlin (0.01-10 microM) for 24-72 hours. Cell lysates are analyzed by Western blot for p53, p21, MDM2, and cleaved PARP. Cell viability is measured by MTT or CellTiter-Glo. Apoptosis is assessed by Annexin V/PI staining. Idasanutlin-d3-1 is used in parallel to quantify drug uptake in treated cells via LC-MS/MS.
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| Animal Protocol |
In xenograft mouse models (e.g., SJSA-1 sarcoma or HCT116 colorectal carcinoma), Idasanutlin is administered orally at doses of 20-50 mg/kg daily for 14-21 days. Tumor volume is measured twice weekly, and tumors are harvested at endpoint for analysis of p53 target gene expression. Plasma and tumor concentrations are quantified using a validated LC-MS/MS method with Idasanutlin-d3-1 as the internal standard. Idasanutlin treatment results in significant tumor growth inhibition.
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| ADME/Pharmacokinetics |
Idasanutlin is orally bioavailable. In preclinical species and humans, it achieves peak plasma concentrations within 1-4 hours after oral administration. The terminal half-life ranges from 4-12 hours. Idasanutlin-d3-1 is used as an internal standard to accurately quantify parent drug levels in plasma and tissue samples. The compound has moderate plasma protein binding and extensive metabolism primarily via CYP3A4, with renal and fecal excretion.
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| Toxicity/Toxicokinetics |
Idasanutlin-d3-1 is used in trace amounts as an analytical standard and does not contribute to toxicity. The unlabeled Idasanutlin has been evaluated in clinical trials. Common adverse events include nausea, vomiting, diarrhea, fatigue, and thrombocytopenia. More severe toxicities such as myelosuppression and gastrointestinal bleeding have been reported at higher doses. The deuterium labeling does not alter the toxicity profile.
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| References | |
| Additional Infomation |
Idasanutlin (RG7388) has been investigated in clinical trials for relapsed or refractory acute myeloid leukemia (AML), neuroblastoma, and other p53-wild-type malignancies. The compound has not yet received regulatory approval. Idasanutlin-d3-1 is a research-grade isotopic standard used exclusively for non-clinical studies. Its deuterium labeling (d3) enables accurate quantitation in mass spectrometry assays with minimal background interference.
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| Molecular Formula |
C31H26D3CL2F2N3O4
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| Molecular Weight |
619.50
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| Related CAS # |
Idasanutlin;1229705-06-9
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| Appearance |
White to off-white solid powder
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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 | 1.6142 mL | 8.0710 mL | 16.1421 mL | |
| 5 mM | 0.3228 mL | 1.6142 mL | 3.2284 mL | |
| 10 mM | 0.1614 mL | 0.8071 mL | 1.6142 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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