| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
CDK4 and CDK6 (cyclin-dependent kinases 4 and 6). Ribociclib-d6 binds to the ATP-binding pocket of CDK4 and CDK6, inhibiting their kinase activity. This prevents the phosphorylation of the retinoblastoma protein (Rb), leading to G1 cell cycle arrest. By blocking the CDK4/6-Rb pathway, Ribociclib-d6 (and its unlabeled parent) inhibits the proliferation of cancer cells, particularly in hormone receptor-positive breast cancer.
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| ln Vitro |
As a labeled internal standard, Ribociclib-d6 is not used for biological activity studies. The unlabeled Ribociclib is a highly potent CDK4/6 inhibitor with IC50 values in the low nanomolar range (approximately 10-50 nM for CDK4 and 10-50 nM for CDK6). It induces G1 cell cycle arrest and apoptosis in cancer cell lines expressing Rb, such as MCF-7 breast cancer cells.
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| ln Vivo |
No specific in vivo activity data has been reported for Ribociclib-d6 as it is an analytical standard. The unlabeled parent drug, Ribociclib, is FDA-approved (Kisqali®) for the treatment of HR+/HER2- advanced or metastatic breast cancer, in combination with an aromatase inhibitor or fulvestrant. It has demonstrated significant improvement in progression-free survival in clinical trials. Ribociclib-d6 is used as an internal standard to accurately measure Ribociclib concentrations in plasma and tissues for PK studies.
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| Enzyme Assay |
Ribociclib-d6 is used as an internal standard in LC-MS/MS assays. A typical protocol involves preparing a calibration curve of unlabeled Ribociclib (target analyte) in blank plasma or tissue homogenate, with a fixed concentration of Ribociclib-d6 (e.g., 10-50 ng/mL) added to each standard, quality control, and study sample. Samples are extracted by protein precipitation (3-4 volumes of acetonitrile containing Ribociclib-d6) or solid-phase extraction. The extract is analyzed by LC-MS/MS in multiple reaction monitoring (MRM) mode, monitoring specific mass transitions for Ribociclib (e.g., m/z 435 → 335) and Ribociclib-d6 (m/z 441 → 341). The concentration of Ribociclib is determined based on the peak area ratio.
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| Cell Assay |
Not applicable. Ribociclib-d6 is an analytical standard and is not used in cell-based assays. The unlabeled Ribociclib is used in cellular studies. MCF-7 or other breast cancer cells are seeded in 96-well plates (5×103 cells/well) and treated with Ribociclib (0.1 nM-10 uM) for 48-96 hours. Cell viability is measured by CellTiter-Glo. Cell cycle distribution is analyzed by flow cytometry after PI staining, and Rb phosphorylation is assessed by Western blotting using a phospho-Rb (Ser780/Ser795) antibody. The labeled compound is used as an internal standard.
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| Animal Protocol |
Ribociclib-d6 is not administered to animals; it is used as a laboratory standard to analyze samples from animals that have been dosed with unlabeled Ribociclib. In a typical PK study, male Sprague-Dawley rats or mice are administered Ribociclib via oral gavage (10-50 mg/kg). Blood samples are collected from the tail vein or by cardiac puncture at multiple time points (0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose). Plasma is separated by centrifugation, and Ribociclib-d6 is added as an internal standard before LC-MS/MS analysis to accurately quantify Ribociclib concentrations. PK parameters (Cmax, Tmax, AUC, t½, oral bioavailability) are calculated by non-compartmental analysis.
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| ADME/Pharmacokinetics |
Ribociclib-d6 has the same PK properties as unlabeled Ribociclib. Ribociclib is well absorbed after oral administration and has moderate oral bioavailability (approximately 50-80%). It is highly bound to plasma proteins (>90%). The compound is metabolized primarily by CYP3A4 to an active metabolite (LEQ506). The half-life in humans is approximately 30-40 hours, allowing for once-daily dosing. The labeled version is used for precise quantification.
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| Toxicity/Toxicokinetics |
Ribociclib-d6 is expected to have the same toxicity profile as unlabeled Ribociclib. The parent drug is generally well-tolerated but can cause dose-limiting toxicities including neutropenia (the most common), leukopenia, nausea, fatigue, diarrhea, and hepatotoxicity (elevated liver enzymes). Monitoring of complete blood counts and liver function tests is recommended during therapy. The labeled isotope is non-radioactive and chemically identical; no additional toxicity is expected.
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| References | |
| Additional Infomation |
Ribociclib-d6 (LEE011-d6) is a stable isotope-labeled internal standard for the quantitative analysis of Ribociclib in biological samples. It contains six deuterium atoms at specific positions in the molecule. The molecular formula is C23H24D6N8O, and the molecular weight is 434.56. The unlabeled parent drug, Ribociclib, has the molecular formula C23H30N8O and a molecular weight of 434.54. The compound is stored at -20degC as a solid and is stable under recommended conditions. It is not for human therapeutic use; it is strictly a research reagent for analytical chemistry.
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| Molecular Formula |
C23H30N8O
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|---|---|
| Molecular Weight |
440.574273586273
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| Exact Mass |
440.291
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| CAS # |
1328934-40-2
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| Related CAS # |
Ribociclib;1211441-98-3;Ribociclib-d6 hydrochloride
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| PubChem CID |
53348205
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
636
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=CC2=CN=C(NC3C=CC(=CN=3)N3CCNCC3)N=C2N1C1CCCC1)N(C([2H])([2H])[2H])C([2H])([2H])[2H]
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| InChi Key |
RHXHGRAEPCAFML-WFGJKAKNSA-N
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| InChi Code |
InChI=1S/C23H30N8O/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28)/i1D3,2D3
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| Chemical Name |
7-cyclopentyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]-N,N-bis(trideuteriomethyl)pyrrolo[2,3-d]pyrimidine-6-carboxamide
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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 | 2.2698 mL | 11.3489 mL | 22.6979 mL | |
| 5 mM | 0.4540 mL | 2.2698 mL | 4.5396 mL | |
| 10 mM | 0.2270 mL | 1.1349 mL | 2.2698 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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