| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
CDK4/CDK6
N-Methyl Palbociclib is an impurity of palbociclib (PD 0332991), which is an orally bioactive, selective CDK4 and CDK6 inhibitor. CDK4/6 are key regulators of the cell cycle, controlling the transition from the G1 phase to the S phase. As an impurity, N-Methyl Palbociclib may retain some structural similarity to the parent drug and could potentially interact with CDK4/6, but its precise binding affinity has not been characterized. |
|---|---|
| ln Vitro |
A pharmacological approach to inhibition of cyclin-dependent kinases 4 and 6 (Cdk4/6) using highly selective small molecule inhibitors has the potential to provide novel cancer therapies for clinical use. Achieving high levels of selectivity for Cdk4/6, versus other ATP-dependent kinases, presents a significant challenge. The pyrido[2,3-d]pyrimidin-7-one template provides an effective platform for the inhibition of a broad cross-section of kinases, including Cdks. It is now demonstrated that the modification of pyrido[2,3-d]pyrimidin-7-ones to include a 2-aminopyridine side chain at the C2-position provides inhibitors with exquisite selectivity for Cdk4/6 in vitro. This selectivity profile is recapitulated in cells where the most selective inhibitors create a G(1) block at concentrations up to 100-fold the IC(50) for cell proliferation. On the basis of its selectivity profile and pharmacokinetic profile, compound 43 (PD 0332991) was identified as a drug candidate for the treatment of cance[1].
As a pharmaceutical impurity, N-Methyl Palbociclib is not tested for standalone in vitro pharmacological activity. Palbociclib, its parent drug, induces G1 phase cell cycle arrest in breast cancer cells (e.g., MCF-7, MDA-MB-231, BT474) by increasing p21 levels and decreasing cyclin E2 expression. The impurity is not expected to have significant independent activity but serves as a control to ensure drug purity and efficacy are not compromised. |
| ln Vivo |
No independent in vivo studies are reported for N-Methyl Palbociclib as a therapeutic agent. As an impurity, it is not administered for pharmacological effect. The in vivo activity of the parent drug palbociclib includes tumor growth inhibition in xenograft models and significant treatment effects in patients with hormone receptor-positive breast cancer. The impurity may be present in trace amounts following drug metabolism or synthesis.
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| Enzyme Assay |
N-Methyl Palbociclib is used in non-cellular analytical method development. It is typically dissolved in an organic solvent such as DMSO or methanol to prepare a stock solution (e.g., 1 mg/mL). The impurity standard is then diluted to working concentrations (e.g., 1-100 ug/mL) and analyzed by high-performance liquid chromatography (HPLC) or LC-MS. Method validation parameters such as linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) are established using this standard.
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| Cell Assay |
For cellular studies, N-Methyl Palbociclib is not used as an independent treatment. Instead, it is used as an analytical standard to quantify the levels of this impurity in cell culture media or lysates from cells treated with palbociclib. After sample collection and protein precipitation, the standard is spiked into the samples at a fixed concentration for LC-MS analysis. The ratio of the impurity to the standard is used for quantification to assess potential metabolic conversion.
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| Animal Protocol |
For in vivo studies, N-Methyl Palbociclib is not typically administered to animals. However, it can be used as an analytical standard for quantifying the impurity in plasma or tissue samples from animals dosed with palbociclib. After sample collection and extraction, the impurity standard is spiked into the samples at a known concentration, followed by LC-MS analysis to determine the concentration of N-Methyl Palbociclib in the biological matrix for ADME and toxicology studies.
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| ADME/Pharmacokinetics |
As a pharmaceutical impurity standard, N-Methyl Palbociclib has no independent pharmacokinetic (PK) parameters. The parent drug palbociclib has an absolute oral bioavailability of approximately 46%, is highly bound to human plasma proteins (∼85%), and has a terminal elimination half-life of approximately 29 hours. The impurity is expected to be present at very low levels relative to the parent drug and would likely follow similar disposition pathways if formed in vivo.
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| Toxicity/Toxicokinetics |
N-Methyl Palbociclib is handled as a reference standard in analytical laboratories. No specific toxicity data is available for this impurity compound. However, for quality control and impurity profiling, acceptable limits are established based on ICH guidelines to ensure patient safety. Standard laboratory safety precautions for handling organic compounds (gloves, safety glasses, fume hood) are recommended when working with this standard. Not intended for human consumption.
|
| References |
[1]. J Med Chem
. 2005 Apr 7;48(7):2388-406. doi: 10.1021/jm049354h.
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| Additional Infomation |
N-Methyl Palbociclib is not a drug but a characterized impurity and analytical standard. It has no approved therapeutic status and is not intended for human use. This compound is used for analytical method development, method validation (AMV), Quality Controlled (QC) application for Abbreviated New Drug Application (ANDA), or during commercial production of palbociclib. It can be used as reference standards with traceability against pharmacopeial standards (USP or EP). Palbociclib itself is an FDA-approved drug for breast cancer.
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| Molecular Formula |
C25H31N7O2
|
|---|---|
| Molecular Weight |
461.56
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| Exact Mass |
461.253
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| CAS # |
571189-51-0
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| PubChem CID |
5330298
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| Appearance |
Typically exists as Light yellow to yellow solids at room temperature
|
| LogP |
2.3
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
803
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCN(CC4)C)C5CCCC5)C(=O)C
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| InChi Key |
PBSZUBKCQUPZFE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H31N7O2/c1-16-20-15-27-25(28-21-9-8-19(14-26-21)31-12-10-30(3)11-13-31)29-23(20)32(18-6-4-5-7-18)24(34)22(16)17(2)33/h8-9,14-15,18H,4-7,10-13H2,1-3H3,(H,26,27,28,29)
|
| Chemical Name |
6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]pyrido[2,3-d]pyrimidin-7-one
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| Synonyms |
N-Methyl Palbociclib; Palbociclib Impurity 87; Pyrido-[2,3-d]-pyrimidin-7-one 55; 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one; 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]pyrido[2,3-d]pyrimidin-7-one; Pyrido[2,3-d]pyrimidin-7(8H)-one, 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-methyl-1-piperazinyl)-2-pyridinyl]amino]-; 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (Palbociclib Impurity);
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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) |
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 | 2.1666 mL | 10.8328 mL | 21.6657 mL | |
| 5 mM | 0.4333 mL | 2.1666 mL | 4.3331 mL | |
| 10 mM | 0.2167 mL | 1.0833 mL | 2.1666 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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