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| 1mg |
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| Other Sizes |
| Targets |
Oclacitinib-13C-d3 targets Janus kinases (JAKs), specifically JAK1. The parent drug Oclacitinib is a potent and selective inhibitor of JAK1, which is involved in signaling pathways for multiple pro-inflammatory and pruritogenic cytokines, including IL-2, IL-4, IL-6, IL-13, and IL-31. By inhibiting JAK1, Oclacitinib blocks the JAK-STAT signaling pathway, thereby reducing cytokine-mediated inflammation and pruritus (itching). The compound also shows some activity against JAK2 and JAK3 at higher concentrations but is selective for JAK1 in therapeutic dose ranges. The deuterium and 13C labeling does not alter the mechanism of action, but the labeled compound is used exclusively as an analytical standard.
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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].
No specific in vitro activity data is provided for Oclacitinib-13C-d3 because it is an analytical standard. The parent compound Oclacitinib has been extensively characterized. Oclacitinib inhibits JAK1 with an IC50 of 10 nM in cell-free enzyme assays, with selectivity over JAK2 (IC50 = 18 nM, 1.8-fold selective) and JAK3 (IC50 = 99 nM, 10-fold selective). In cellular assays using canine peripheral blood mononuclear cells (PBMCs), Oclacitinib inhibits IL-31-induced STAT phosphorylation with an IC50 of approximately 50 nM. The compound also inhibits the production of IL-31 from stimulated T cells. The in vitro potency correlates with its anti-pruritic effects in vivo. The compound has a favorable selectivity profile for JAK1 over other JAK family members. |
| ln Vivo |
No specific in vivo data is provided for Oclacitinib-13C-d3. The parent drug Oclacitinib is used in veterinary medicine. In dogs with atopic dermatitis, oral administration of Oclacitinib (0.4-0.6 mg/kg twice daily) rapidly reduces pruritus within 24 hours. In preclinical studies in rodents, Oclacitinib reduces inflammation in models of allergic contact dermatitis and reduces clinical signs in a canine model of atopic dermatitis. The compound is well-tolerated in dogs, with the most common adverse effects being mild gastrointestinal signs (vomiting, diarrhea). The label specifies that it is not for use in humans. The labeled internal standard is used for quantification in PK studies of Oclacitinib.
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| Enzyme Assay |
Oclacitinib-13C-d3 is not used in cell-free or cell-based assays for target engagement. It is used as an internal standard in analytical chemistry. For LC-MS/MS method validation, calibration standards are prepared by spiking known concentrations of non-labeled Oclacitinib into blank biological matrix (e.g., canine plasma, serum, or tissue homogenate). A fixed concentration of Oclacitinib-13C-d3 (e.g., 10-100 ng/mL) is added to each calibrator, QC sample, and study sample. Samples are prepared by protein precipitation with acetonitrile or methanol containing the internal standard. After centrifugation, the supernatant is injected onto a reversed-phase HPLC column coupled to a triple quadrupole mass spectrometer operated in positive ion electrospray mode (ESI+). MRM transitions: parent drug m/z 338.0 → m/z 197.0; internal standard m/z 342.0 → m/z 199.0 (for 13C-d3). The peak area ratio (analyte/IS) is used for quantification.
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| Cell Assay |
Oclacitinib-13C-d3 is not typically used in cellular assays. For studies of Oclacitinib pharmacology, a cellular assay using canine PBMCs is used. PBMCs are isolated from dog whole blood by density gradient centrifugation. Cells are seeded in 96-well plates (2×10⁵ cells/well) in RPMI-1640 medium with 10% FBS. Cells are treated with Oclacitinib (0.1-1000 nM) for 30 minutes, then stimulated with IL-31 (100 ng/mL) for 15 minutes. Cells are lysed, and STAT3 phosphorylation is measured by phospho-STAT3 ELISA or by Western blotting with phospho-specific antibodies. Alternatively, for proliferation assays, PBMCs are stimulated with PHA (phytohemagglutinin, 5 microg/mL) in the presence of Oclacitinib (1-1000 nM) for 72 hours, and proliferation is measured by [3H]-thymidine incorporation or CFSE dilution. Oclacitinib-13C-d3 is not used in these assays.
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| Animal Protocol |
In vivo studies for Oclacitinib are typically conducted in dogs or rodents. For a PK study, male Beagle dogs (n=4-6) are fasted overnight and then administered Oclacitinib maleate (0.4-0.6 mg/kg) orally as a single dose. Blood samples are collected from the jugular vein at pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose. Plasma is separated by centrifugation. Oclacitinib concentrations are quantified by LC-MS/MS using Oclacitinib-13C-d3 as internal standard. PK parameters (Cmax, Tmax, AUC, t½, oral bioavailability) are calculated. In a repeated dose toxicity study, dogs receive Oclacitinib daily for 28 days. Blood samples are collected for PK analysis and for hematology, serum chemistry, and coagulation profiles. Tissue samples are collected at necropsy for histopathology. The labeled internal standard is used for quantification of drug concentrations in plasma and tissues.
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| ADME/Pharmacokinetics |
Oclacitinib-13C-d3 has a molecular formula of C14[13C]H20D3N5O2S and a molecular weight of 341.45 g/mol (free base). The compound is supplied as a solid and should be stored at -20degC in a sealed container, protected from light and moisture, where it is stable for up to 3 years. For solution storage, stock solutions in DMSO or methanol should be stored at -80degC for up to 6 months. The compound is soluble in DMSO and methanol. For analytical use, working solutions are prepared by dilution in acetonitrile/water (50:50) or mobile phase. The internal standard is typically added to samples at a concentration of 10-100 ng/mL, depending on the expected analyte concentration range. The product is for research use only, not for human use.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic use. Oclacitinib is approved for veterinary use in dogs under the brand name Apoquel. The safety and efficacy of Oclacitinib in humans have not been established. The deuterated and 13C-labeled internal standard poses minimal risk at the concentrations used in analytical methods. Standard laboratory safety practices (gloves, lab coat, safety glasses) should be followed. Avoid inhalation of powder. This product is not an FDA-approved drug. It is intended for use as an internal standard in research applications only. Supplier information must not be included.
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| References | |
| Additional Infomation |
Oclacitinib is a JAK1 inhibitor that was developed for the treatment of pruritus and inflammation associated with allergic dermatitis and atopic dermatitis in dogs. It is not approved for use in humans. Oclacitinib-13C-d3 is synthesized by replacing specific carbon atoms with carbon-13 (13C) and hydrogen atoms with deuterium (d3). This stable isotope-labeled internal standard is used for accurate quantification of Oclacitinib in biological matrices by MS methods, correcting for matrix effects and variability in sample preparation. The compound is typically >99% enriched in 13C and 99% deuterated forms (d1-d3). This product is not a drug and is for research use only. Supplier information must not be included.
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| Molecular Formula |
C1413CH20D3N5O2S
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| Molecular Weight |
341.45
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| Related CAS # |
Oclacitinib;1208319-26-9
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| Appearance |
White to off-white 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 |
| 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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9287 mL | 14.6434 mL | 29.2869 mL | |
| 5 mM | 0.5857 mL | 2.9287 mL | 5.8574 mL | |
| 10 mM | 0.2929 mL | 1.4643 mL | 2.9287 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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