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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Ribociclib-d6 hydrochloride targets CDK4 and CDK6, which are crucial for cell cycle progression from the G1 phase to the S phase. Ribociclib binds to the ATP-binding site of CDK4/6, preventing their activation. The deuterated version has the same mechanism. The parent compound has IC50 values of 10 nM for CDK4 and 39 nM for CDK6, with over 1,000-fold selectivity against the cyclin B/CDK1 complex.
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| ln Vitro |
In vitro, Ribociclib-d6 hydrochloride is a deuterated compound and is used as a tracer. The parent compound, Ribociclib, specifically inhibits CDK4 and CDK6 activity, leading to G1 phase cell cycle arrest in cancer cells. It effectively halts proliferation in cancer models by blocking these kinases. The compound is highly specific, with over 1,000-fold selectivity against the cyclin B/CDK1 complex.
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| ln Vivo |
In vivo, Ribociclib reduces tumor growth in hormone receptor-positive breast cancer models. The deuterated version is used as an internal standard for pharmacokinetic studies to quantify Ribociclib levels in plasma and tissues. Ribociclib is clinically approved for the treatment of HR+/HER2- breast cancer. The labeling does not alter efficacy but allows for precise tracking.
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| Enzyme Assay |
A cell-free enzyme inhibition assay for Ribociclib is performed using purified CDK4/Cyclin D1 or CDK6/Cyclin D3 complexes. The enzyme (0.5-1 microg) is incubated with varying concentrations of Ribociclib-d6 hydrochloride (0.1-1000 nM) in kinase buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.01% Triton X-100). The reaction is initiated by adding 50 microM ATP and a peptide substrate (e.g., GST-Rb). After 30-60 min at 30degC, the reaction is stopped. Phosphorylated substrate is detected using a specific antibody in an ELISA or by measuring 32P incorporation. The IC50 is calculated.
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| Cell Assay |
MCF-7 or T47D breast cancer cells are seeded in 96-well plates (5,000-10,000 cells/well) in RPMI-1640 + 10% FBS. After 24 h, cells are treated with Ribociclib-d6 hydrochloride (0.1-1000 nM) for 48-96 h. Cell viability is measured by MTT or CellTiter-Glo assay. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. Ribociclib induces G1 phase arrest. For deuterated compound, LC-MS/MS is used to measure cellular uptake.
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| Animal Protocol |
Ribociclib-d6 hydrochloride is used as an internal standard for PK studies. Female BALB/c nude mice (6-8 weeks, 18-22 g) are implanted with MCF-7 cells. When tumors reach 100-200 mm3, mice are administered a single oral dose of Ribociclib (10-50 mg/kg). Blood samples are collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24 h. A fixed concentration of Ribociclib-d6 hydrochloride is added to each plasma sample as an internal standard. Samples are extracted and analyzed by LC-MS/MS. PK parameters are calculated using non-compartmental analysis.
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| ADME/Pharmacokinetics |
Ribociclib-d6 hydrochloride has a molecular formula of C23H25D6ClN8O and a molecular weight of 477.0 g/mol. The product should be stored at -20degC for up to 3 years or at 4degC for up to 2 years. In solvent, it is stable for 1 year at -80degC or 1 month at -20degC. The deuterium labeling enhances stability and allows for precise tracking in metabolic studies. Specific PK parameters are available for the parent compound (t½ ~ 28-32 h in humans).
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| Toxicity/Toxicokinetics |
Ribociclib is generally well-tolerated in clinical settings. Common adverse effects include neutropenia, nausea, fatigue, and QT prolongation. The deuterated version is used in trace amounts as an analytical standard and does not pose additional safety risks. Standard safety precautions for handling CDK4/6 inhibitors should be followed. Ribociclib-d6 hydrochloride is for research use only.
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| References |
[1]. VanArsdale T, et al. Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment. Clin Cancer Res. 2015 Jul 1;21(13):2905-10.
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| Additional Infomation |
Ribociclib-d6 hydrochloride is a research-grade stable isotope-labeled compound and is not approved for clinical use. It is used as an internal standard for the quantification of Ribociclib, a specific CDK4/6 inhibitor for hormone receptor-positive breast cancer. This product is for research use only and not for human therapeutic applications. Store as a powder at -20degC.
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| Molecular Formula |
C23H25D6CLN8O
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| Related CAS # |
Ribociclib;1211441-98-3;Ribociclib hydrochloride;1211443-80-9;Ribociclib succinate;1374639-75-4;Ribociclib succinate hydrate;1374639-79-8;Ribociclib-d6;1328934-40-2
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO :~100 mg/mL (~209.63 mM)
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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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