| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Upadacitinib is a potent, orally bioavailable, and selective inhibitor of JAK1 with an IC₅0 of 43 nM in enzyme assays. It shows approximately 74‑fold selectivity for JAK1 over JAK2 (IC₅0 200 nM) in cellular assays. JAK1 is a non‑receptor tyrosine kinase that transduces signals from cytokines such as IL‑2, IL‑4, IL‑6, and interferon‑gamma, leading to the activation of STAT transcription factors and inflammation‑related gene expression.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an impact on a drug's pharmacokinetics and metabolic profile, it has drawn attention [1].
The labeled compound is used only as a tracer and is not tested for activity. Upadacitinib itself inhibits JAK1‑dependent signaling in vitro: in T‑cell lines stimulated with IL‑2, upadacitinib blocks STAT5 phosphorylation with an IC₅0 of 20‑50 nM. In whole blood assays from rheumatoid arthritis patients, upadacitinib inhibits IL‑6‑induced STAT3 and STAT1 phosphorylation with similar potency. |
| ln Vivo |
Upadacitinib produces dose‑dependent anti‑inflammatory effects in animal models of arthritis, colitis, and psoriasis. For example, in a rat adjuvant‑induced arthritis model, oral upadacitinib (0.1‑10 mg/kg, once daily) significantly reduces paw swelling, joint inflammation, and bone resorption. The effect is comparable to or better than first‑generation JAK inhibitors. The labeled version is not administered for efficacy studies.
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| Enzyme Assay |
A typical kinase inhibition assay uses recombinant JAK1 enzyme and a peptide substrate. The reaction is performed in 384‑well plates with upadacitinib (0.01‑1000 nM) in the presence of ATP (10 uM to the Km value). After 30‑60 minutes, the reaction is stopped by adding EDTA. The amount of phosphorylated substrate is measured by a homogeneous time‑resolved fluorescence (HTRF) assay. The IC₅0 is determined by fitting the inhibition curve. For the labeled form, no such assay is performed.
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| Cell Assay |
Cellular selectivity is determined in cell lines (e.g., HEL cells or Ba/F3 cells transformed with JAK1, JAK2, or TYK2 fusions). Cells are seeded in 96‑well plates and treated with upadacitinib (0.1‑1000 nM). After 1 hour, the cells are stimulated with the appropriate cytokine (e.g., IL‑6 for JAK1). STAT phosphorylation is measured by flow cytometry (phospho‑STAT flow) or by Western blotting. The labeled form is not used in these assays.
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| Animal Protocol |
The labeled compound is used in pharmacokinetic studies of upadacitinib. Typically, Sprague‑Dawley rats or beagle dogs receive an oral or intravenous dose of upadacitinib (1‑10 mg/kg). Serial blood samples are collected, and plasma is processed. Upadacitinib‑¹⁵N,d2 is added to the calibration standards, quality controls, and study samples as an internal standard. LC‑MS/MS analysis in positive ion mode with multiple reaction monitoring (MRM) of the m/z transition specific to the compound and its labeled version is performed.
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| ADME/Pharmacokinetics |
The deuterium and nitrogen‑15 labeling results in a +3 Da mass shift but does not alter the physicochemical properties (solubility, pKa, logP) or the pharmacokinetics of upadacitinib when used at trace levels. Upadacitinib itself has high oral bioavailability (>80% in rats and humans), low plasma protein binding (≈20%), and a terminal elimination half‑life of 8‑14 hours. It is primarily metabolized by CYP3A4.
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| Toxicity/Toxicokinetics |
Upadacitinib is generally safe and well‑tolerated in humans when used at the approved doses (15 mg or 30 mg once daily). Common side effects include upper respiratory tract infections, nausea, and acne. Serious adverse events include opportunistic infections (e.g., herpes zoster) and, rarely, thromboembolic events. The labeled internal standard is not administered to humans.
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| Additional Infomation |
Upadacitinib (Rinvoq) received FDA approval in 2019 for moderate‑to‑severe rheumatoid arthritis in adults who have had an inadequate response to methotrexate. Since then, approvals have expanded to psoriatic arthritis, atopic dermatitis, ulcerative colitis, and ankylosing spondylitis. Upadacitinib‑¹⁵N,d2 is an essential reagent for therapeutic drug monitoring, bioequivalence studies, and preclinical pharmacokinetics. The stable isotope labeling enables high‑sensitivity and high‑specificity quantification.
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| Molecular Formula |
C17H17D2F3N515NO
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|---|---|
| Molecular Weight |
383.37
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| Related CAS # |
Upadacitinib;1310726-60-3;Upadacitinib tartrate tetrahydrate;1607431-21-9
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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 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 | 2.6084 mL | 13.0422 mL | 26.0845 mL | |
| 5 mM | 0.5217 mL | 2.6084 mL | 5.2169 mL | |
| 10 mM | 0.2608 mL | 1.3042 mL | 2.6084 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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