| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
CDK4 (Cyclin-dependent kinase 4), CDK6 (Cyclin-dependent kinase 6)
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
This deuterated compound is a potent inhibitor of CDK4 and CDK6, with IC50 values in the range of 1-3 nM. Its mechanism of action is to inhibit the phosphorylation of the retinoblastoma (Rb) protein, thereby preventing cell cycle progression from the G1 to the S phase. It exhibits potent anti-tumor activity. |
| ln Vivo |
As a primary metabolite of abemaciclib, it contributes to the overall pharmacological activity of the parent drug. In vivo, it is expected to have similar or improved antitumor activity compared to the parent. Its longer half-life can lead to sustained target inhibition. This metabolite can be used to design PROTAC CDK4/6 degraders.
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| Enzyme Assay |
In a non-cellular kinase assay, recombinant human CDK4/Cyclin D1 or CDK6/Cyclin D3 enzymes are incubated with the substrate, retinoblastoma protein (Rb), and ATP in a reaction buffer. The internal standard, M2-d6, is included in the sample processing. After the reaction, the amount of phosphorylated Rb substrate is measured using a specific antibody in an ELISA or by a radiometric filter binding assay.
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| Cell Assay |
For in vitro cell proliferation assays, cancer cell lines (e.g., MCF-7 or T-47D) are seeded in 96-well plates. The cells are treated with varying concentrations of the unlabeled abemaciclib metabolite M2 for 72-120 hours. Cell viability is assessed using the CellTiter-Glo® Luminescent Cell Viability Assay to measure ATP content. IC50 values are calculated to determine the potency of the metabolite.
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| Animal Protocol |
In a xenograft model, nude mice are subcutaneously implanted with human tumor cells (e.g., Colo-205 colorectal carcinoma). Once the tumors reach a certain size, the mice are administered abemaciclib or its metabolite via oral gavage. The unlabeled compound's concentration in plasma and tumor is determined using LC-MS with the deuterated internal standard. Tumor volumes are measured, and the TGI is calculated.
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| ADME/Pharmacokinetics |
In humans, abemaciclib is metabolized to several active metabolites, including M2 and M18. M2 has a similar potency to the parent drug but a significantly longer half-life (~30 hours vs. ~18 hours for abemaciclib). It is a major contributor to the overall pharmacological effect. This metabolite is also susceptible to deuteration, which can alter its PK.
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| Toxicity/Toxicokinetics |
Abemaciclib is an FDA-approved drug for breast cancer (Verzenio®). The parent drug's toxicity profile includes diarrhea, neutropenia, nausea, and fatigue. The M2 metabolite is expected to contribute to these toxicities, particularly to myelosuppression (neutropenia). The deuterated form is a research tool with no intended human use.
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| References | |
| Additional Infomation |
CDK4/6 inhibitors have revolutionized the treatment of HR+/HER2- breast cancer. Abemaciclib differs from other CDK4/6 inhibitors by its ability to cross the blood-brain barrier. The active metabolite M2 is a key reason for its sustained activity. This deuterated product is used for precise pharmacokinetic studies of the metabolite.
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| Molecular Formula |
C25H22D6F2N8
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|---|---|
| Molecular Weight |
484.58
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| Related CAS # |
Abemaciclib metabolite M2;1231930-57-6
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| Appearance |
Off-white to light yellow 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 :~2.12 mg/mL (~4.37 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0636 mL | 10.3182 mL | 20.6364 mL | |
| 5 mM | 0.4127 mL | 2.0636 mL | 4.1273 mL | |
| 10 mM | 0.2064 mL | 1.0318 mL | 2.0636 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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