| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Lumacaftor-d4 shares the same molecular target as its non-deuterated form, lumacaftor. Lumacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) corrector that binds to the first nucleotide-binding domain of CFTR and facilitates the proper folding and trafficking of the mutant F508del-CFTR protein to the cell surface. The labeled compound is used as an internal standard for the quantification of lumacaftor in biological samples.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers that influence measurement during the drug development process. It's possible that the pharmacokinetics and functional range of medications contribute to the concern over mutagenesis [1].
The labeled compound itself does not possess intrinsic pharmacological activity in vitro; its biological activity is identical to that of lumacaftor. Lumacaftor has been shown to correct the folding and trafficking of F508del-CFTR in cell-based assays. The labeled compound is used as an internal standard for quantifying lumacaftor in biological samples, not for evaluating its own pharmacological activity. |
| ln Vivo |
Lumacaftor-d4 is not used as a therapeutic agent; its non-deuterated form, lumacaftor, is used in combination with ivacaftor for the treatment of cystic fibrosis in patients with the F508del mutation. In vivo, lumacaftor is absorbed after oral administration and metabolized in the liver. The labeled compound is used in pharmacokinetic studies to accurately measure lumacaftor concentrations in plasma and other biological matrices.
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| Enzyme Assay |
In vitro receptor binding assays for lumacaftor-d4 are not standard, as it is an analytical standard. The CFTR-correcting activity of its non-deuterated form is assessed using cell-based assays measuring CFTR-mediated chloride transport. The labeled compound is used as an internal standard for LC-MS/MS analysis of lumacaftor concentrations in biological samples. Quality control includes purity analysis (>95%).
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| Cell Assay |
In vitro cell culture experiments are not performed with lumacaftor-d4. When studying the effects of lumacaftor in cellular systems, the non-labeled compound is used. Cells expressing F508del-CFTR are treated with lumacaftor, and CFTR trafficking and function are measured. The labeled compound is used as an internal standard for LC-MS/MS analysis.
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| Animal Protocol |
In vivo animal studies are not conducted with lumacaftor-d4. When used in pharmacokinetic studies, the labeled compound serves as an internal standard for the quantification of lumacaftor in animal plasma or tissue samples.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of lumacaftor-d4 itself are not characterized, as it is not a drug substance. Lumacaftor has a bioavailability of approximately 30-40% after oral administration, with a half-life of 20-30 hours in humans. It is metabolized primarily by cytochrome P450 3A4. The labeled compound is used as an internal standard to accurately quantify lumacaftor in pharmacokinetic studies.
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| Toxicity/Toxicokinetics |
Lumacaftor-d4 is not a therapeutic agent and has not been evaluated for toxicity in humans. Its non-deuterated form, lumacaftor, is generally well-tolerated, with common side effects including respiratory events, nausea, and diarrhea. The deuterated compound is for research use only and should be handled with standard laboratory precautions.
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| References | |
| Additional Infomation |
Lumacaftor-d4 is a stable isotope-labeled internal standard used in pharmacokinetic and metabolic studies of lumacaftor. It is also known as VX-809-d4 and VRT 826809-d4. The compound is used in analytical method development, method validation, and quality control applications for generic drug products. The incorporation of deuterium allows for accurate quantification of lumacaftor in biological samples using mass spectrometry.
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| Molecular Formula |
C24H18F2N2O5
|
|---|---|
| Molecular Weight |
452.406933307648
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| Exact Mass |
456.143
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| CAS # |
2733561-44-7
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| Related CAS # |
Lumacaftor;936727-05-8
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| PubChem CID |
166642625
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
|
| Complexity |
776
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1(C(C1(C2=CC3=C(C=C2)OC(O3)(F)F)C(=O)NC4=NC(=C(C=C4)C)C5=CC(=CC=C5)C(=O)O)([2H])[2H])[2H]
|
| InChi Key |
UFSKUSARDNFIRC-YQUBHJMPSA-N
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| InChi Code |
InChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)/i9D2,10D2
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| Chemical Name |
3-[3-methyl-6-[[2,2,3,3-tetradeuterio-1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino]pyridin-2-yl]benzoic acid
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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 | 2.2104 mL | 11.0519 mL | 22.1038 mL | |
| 5 mM | 0.4421 mL | 2.2104 mL | 4.4208 mL | |
| 10 mM | 0.2210 mL | 1.1052 mL | 2.2104 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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