| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
BCR-ABL fusion tyrosine kinase, c-KIT, and PDGFR. N-Desmethyl imatinib retains the ability to compete with ATP for binding to the kinase domain of BCR-ABL, inhibiting the constitutively active tyrosine kinase in CML. The metabolite also inhibits other tyrosine kinases, including c-KIT and PDGFR-alpha/beta, albeit with lower potency compared to the parent drug imatinib.
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|---|---|
| ln Vitro |
Imatinib, the parent drug, inhibits BCR-ABL with an IC50 of 0.025-0.27 uM in cell-based assays. The N-desmethyl metabolite is equipotent to imatinib in biochemical kinase assays but has slightly reduced activity in cellular proliferation assays due to lower cellular uptake. It is still a pharmacologically active metabolite that contributes to overall therapeutic efficacy, particularly at steady state due to its longer half-life.
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| ln Vivo |
Imatinib (50-100 mg/kg orally) in xenograft mouse models of CML (K562) produces significant tumor growth inhibition. The N-desmethyl metabolite, while less potent than imatinib, reaches substantial plasma concentrations (approximately 15-20% of parent drug levels in humans). In vivo, it contributes to the overall inhibition of BCR-ABL kinase activity, especially during chronic daily dosing due to its accumulation.
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| Enzyme Assay |
Radioligand binding assays for BCR-ABL kinase are performed using the time-resolved fluorescence resonance energy transfer (TR-FRET) method. Recombinant human BCR-ABL kinase (1-5 nM) is incubated with varying concentrations of N-Desmethyl imatinib D8 (0.1-1000 nM) in 50 mM HEPES buffer (pH 7.5) containing 10 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.01% BSA, and 10 uM ATP for 60 min at 25degC. Phosphorylation of the substrate peptide is detected using an Eu-labeled antibody. IC50 values are calculated.
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| Cell Assay |
K562 human leukemia cells are cultured in RPMI-1640 medium supplemented with 10% FBS and 1% penicillin/streptomycin. Cells (1 × 10⁵ cells/well) are seeded into 96-well plates. Varying concentrations of N-Desmethyl imatinib (0.01-50 uM) are added, and the plates are incubated for 48-72 h at 37degC, 5% CO2. Cell viability is measured using the MTT assay (absorbance at 570 nm) or the CellTiter-Glo assay. The IC50 for inhibition of proliferation is calculated by non-linear regression.
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| Animal Protocol |
Not applicable (primarily an internal standard, not a test article in efficacy studies). However, in rat PK studies: Male Wistar rats are dosed orally with Imatinib (10-30 mg/kg). Blood samples are collected via tail vein at pre-dose and 0.5, 1, 2, 4, 8, 12, 24 h post-dose. N-Desmethyl imatinib D8 is used as the internal standard in the LC-MS/MS method. Plasma is protein-precipitated with acetonitrile, and the supernatant is injected onto a C18 column for quantification of both Imatinib and its metabolite.
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| ADME/Pharmacokinetics |
N-Desmethyl imatinib D8 serves as an internal standard (IS) for bioanalysis. The parent drug imatinib has an oral bioavailability of ~98%, is highly protein bound (~95%), and has a terminal half-life of ~18 h (humans). The N-desmethyl metabolite is primarily formed by CYP3A4, has a longer half-life (~40 h) than the parent drug, and contributes to net inhibition.
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| Toxicity/Toxicokinetics |
The D8-labeled compound is not administered to humans. The parent drug imatinib is generally well tolerated but common AEs include edema (periorbital, peripheral), nausea, muscle cramps, rash, and diarrhea. Serious AEs: myelosuppression (neutropenia, thrombocytopenia), hepatotoxicity (elevated LFTs, rare liver failure), and fluid retention (pleural effusion, pericardial effusion, ascites).
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| Additional Infomation |
Imatinib (Gleevec) was FDA-approved in 2001, revolutionizing the treatment of CML. N-Desmethyl imatinib D8 is a research internal standard for LC-MS/MS bioanalysis, enabling the accurate determination of the pharmacokinetic profiles of imatinib and its active metabolite. It is essential for therapeutic drug monitoring (TDM) studies, bioequivalence trials, and drug-drug interaction investigations involving CYP3A4-modulating drugs.
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| Molecular Formula |
C₂₈H₂₁D₈N₇O
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|---|---|
| Molecular Weight |
487.63
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| Exact Mass |
487.294
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| CAS # |
1185103-28-9
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| Related CAS # |
N-Desmethyl imatinib;404844-02-6;N-Desmethyl imatinib mesylate;404844-03-7;N-Desmethyl imatinib-d4
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| PubChem CID |
44816894
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.66
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
679
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1(C(N(C(C(N1)([2H])[2H])([2H])[2H])CC2=CC=C(C=C2)C(=O)NC3=CC(=C(C=C3)C)NC4=NC=CC(=N4)C5=CN=CC=C5)([2H])[2H])[2H]
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| InChi Key |
BQQYXPHRXIZMDM-DBVREXLBSA-N
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| InChi Code |
InChI=1S/C28H29N7O/c1-20-4-9-24(17-26(20)34-28-31-12-10-25(33-28)23-3-2-11-30-18-23)32-27(36)22-7-5-21(6-8-22)19-35-15-13-29-14-16-35/h2-12,17-18,29H,13-16,19H2,1H3,(H,32,36)(H,31,33,34)/i13D2,14D2,15D2,16D2
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| Chemical Name |
N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]-4-[(2,2,3,3,5,5,6,6-octadeuteriopiperazin-1-yl)methyl]benzamide
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| Synonyms |
N Desmethyl imatinib D8 N-Desmethyl imatinib D8
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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 | 2.0507 mL | 10.2537 mL | 20.5074 mL | |
| 5 mM | 0.4101 mL | 2.0507 mL | 4.1015 mL | |
| 10 mM | 0.2051 mL | 1.0254 mL | 2.0507 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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