| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Ponatinib D8 targets the same multi-targeted kinases as Ponatinib. Ponatinib is an orally active multi-targeted kinase inhibitor with IC50 values of 0.37 nM for Abl, 1.1 nM for PDGFRα, 1.5 nM for VEGFR2, 2.2 nM for FGFR1, and 5.4 nM for Src. It is used for the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), including T315I-positive cases. The deuterium labeling does not significantly alter target binding.
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| ln Vitro |
In vitro studies with Ponatinib D8 primarily focus on its use as an analytical internal standard rather than its pharmacological activity. The compound is used in LC-MS/MS methods for the quantification of Ponatinib in biological matrices. The deuterium labeling provides a mass shift that allows differentiation from the unlabeled compound, enabling accurate quantification. The compound's in vitro activity at multi-targeted kinases is expected to be similar to that of unlabeled Ponatinib.
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| ln Vivo |
In vivo studies using Ponatinib D8 are primarily pharmacokinetic, where the compound serves as an internal standard for the quantification of Ponatinib in biological samples. The deuterium-labeled compound can be co-administered with unlabeled Ponatinib to study absorption, distribution, metabolism, and excretion. It has been used in bioequivalence studies and method validation for regulatory submissions. Its in vivo pharmacological effects are expected to be similar to those of Ponatinib, a multi-targeted kinase inhibitor used for the treatment of CML and ALL.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for Ponatinib D8 are typically performed as part of analytical method validation rather than pharmacological characterization. The compound is used as an internal standard in LC-MS/MS assays for the quantification of Ponatinib. Kinase inhibition assays can be performed using recombinant kinases and peptide substrates, but the deuterated compound is primarily used for analytical purposes. The compound is dissolved in appropriate solvents and spiked into biological matrices at known concentrations. Calibration curves are generated by plotting the peak area ratio of Ponatinib to Ponatinib D8 against the concentration of Ponatinib.
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| Cell Assay |
For in vitro cell-based assays, Ponatinib D8 can be used in studies investigating Ponatinib's cellular effects. Cancer cell lines expressing Bcr-Abl or other Ponatinib targets are cultured in appropriate media and treated with the compound. Kinase inhibition is confirmed by measuring the phosphorylation of downstream signaling proteins via Western blot. Cell viability and proliferation are assessed by MTT or CellTiter-Glo assays. However, the compound's primary use is as an analytical internal standard.
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| Animal Protocol |
In vivo animal studies with Ponatinib D8 are primarily pharmacokinetic. The compound is administered orally to rodents at doses determined from pharmacokinetic studies, and blood samples are collected at predetermined time points. Plasma concentrations of both labeled and unlabeled Ponatinib are analyzed by LC-MS/MS using Ponatinib D8 as the internal standard. For pharmacodynamic studies, the compound's effects on tumor growth and kinase inhibition can be evaluated in appropriate animal models. The deuterium labeling may affect the compound's metabolic stability, potentially altering its pharmacokinetic profile.
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| ADME/Pharmacokinetics |
Ponatinib D8 has a molecular weight of 540.61 g/mol and molecular formula C29H27F3N6O. Chemical name: 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-(4-((2,2,3,3,5,5,6,6-octadeutero-4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide. The compound is a deuterium-labeled analog of Ponatinib. Pharmacokinetic properties are expected to be similar to Ponatinib. Ponatinib D8 is used in very small quantities as an analytical internal standard.
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| Toxicity/Toxicokinetics |
As a deuterium-labeled analogue of an approved drug, Ponatinib D8 is expected to have a similar toxicity profile to Ponatinib, though toxicity studies are typically not performed on the labeled compound due to its use as an analytical standard. Ponatinib has side effects including hypertension, rash, abdominal pain, and fatigue. Ponatinib D8 is used in very small quantities as an analytical internal standard and does not pose significant toxicity risks under normal handling.
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| References | |
| Additional Infomation |
Ponatinib D8 is a deuterium-labeled form of Ponatinib, an orally active multi-targeted kinase inhibitor. It has a molecular weight of 540.61 g/mol and molecular formula C29H27F3N6O. The compound is used as an internal standard for analytical method development, method validation, quality control applications for abbreviated new drug applications, or during commercial production of Ponatinib. Ponatinib inhibits Abl, PDGFRα, VEGFR2, FGFR1, and Src with IC50 values of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM, respectively. Ponatinib D8 is not intended for therapeutic use and is for research and analytical use only.
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| Molecular Formula |
C₂₉H₁₉D₈F₃N₆O
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|---|---|
| Molecular Weight |
540.61
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| Exact Mass |
540.27
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| CAS # |
1562993-37-6
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| Related CAS # |
Ponatinib;943319-70-8
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| PubChem CID |
73214034
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| Appearance |
White to light yellow solid powder
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| LogP |
4.404
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
39
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| Complexity |
910
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1(C(N(C(C(N1C)([2H])[2H])([2H])[2H])CC2=C(C=C(C=C2)NC(=O)C3=CC(=C(C=C3)C)C#CC4=CN=C5N4N=CC=C5)C(F)(F)F)([2H])[2H])[2H]
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| InChi Key |
PHXJVRSECIGDHY-DHNBGMNGSA-N
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| InChi Code |
InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)/i12D2,13D2,14D2,15D2
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| Chemical Name |
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(2,2,3,3,5,5,6,6-octadeuterio-4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
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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 | 1.8498 mL | 9.2488 mL | 18.4976 mL | |
| 5 mM | 0.3700 mL | 1.8498 mL | 3.6995 mL | |
| 10 mM | 0.1850 mL | 0.9249 mL | 1.8498 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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