Upadacitinib (Synonyms: ABT-494) |
Catalog No.GC19368
One-Click Copy Product Info
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Upadacitinib is a highly potent, orally administered, and reversible selective Janus kinase 1 (JAK1) inhibitor with an IC50 value of 0.043μM .
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1310726-60-3
Sample solution is provided at 25 µL, 10mM.
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Upadacitinib is a highly potent, orally administered, and reversible selective Janus kinase 1 (JAK1) inhibitor with an IC50 value of 0.043μM [1]. Upadacitinib has been shown to effectively alleviate the symptoms of rheumatoid arthritis [2,3].
In vitro studies have demonstrated that the IC50 values of Upadacitinib for JAK1, JAK2, JAK3 and TYK2 in Ba/F3 cells are 0.045μM, 0.109μM, 2.1μM and 4.7μM. Upadacitinib selectively inhibits JAK1-dependent cytokines the expression in Ba/F3 cells, including IL-6, IL-2 and IFNγ, thereby contributing to the improvement of rheumatoid arthritis [4].
In vivo experiments revealed that Upadacitinib, when administered via oral gavage twice daily at doses of 0.1, 0.3, 1, 3 and 10mg/kg for 10 days to rats with arthritis induced by mycobacterial adjuvant injection into the right hind footpad, significantly reduced joint inflammation and improved joint tissue damage in the 1, 3 and 10mg/kg treatment groups [4].
References:
[1]European Medicines Agency . Rinvoq (upadacitinib) assessment report. Procedure No. EMEA/H/C/004760/0000 (EMA/608624/2019 Corr. 1). 2020.
[2]RINVOQ™ (Upadacitinib) [US package insert]. North Chicago, IL: AbbVie Inc., 2019.
[3]Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. 2019 Nov;71(11):1788-1800.
[4]Parmentier JM, Voss J, Graff C, et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT‐494). BMC Rheumatol. 2018;2:23.
| Cell experiment [1]: | |
Cell lines | Ba/F3 cells |
Preparation Method | Ba/F3 cells were washed and resuspended in Hank’s balanced salt solution at a density of 2x107 cells/mL. Five microliters of cell suspension were added to a 384-well, low-volume, white-walled polystyrene plate that contained 5μL of Upadacitinib. Cells were incubated with compound (final DMSO concentration 0.5%) for 30min at 37℃ before proceeding with pSTAT5 detection. |
Reaction Conditions | 0, 0.01, 0.1, 0.5, 1, 2μM; |
Applications | Upadacitinib exhibited greater than 40-fold selectivity for JAK1 (IC50 = 0.045μM) compared to JAK2 (IC50 = 0.109μM) and demonstrated significant selectivity against JAK3 (approximately 130-fold) and TYK2 (approximately 190-fold). |
| Animal experiment [1,2]: | |
Animal models | Female Lewis rats |
Preparation Method | Arthritis was induced in female Lewis rats (weight, 125 – 150 g)by a single intradermal injection of 0.1mL of microbacterium tuberculosis emulsion into the right hind footpad (Day 0). Rats were dosed as indicated orally by gavage twice a day for 10 days (Day7 – Day17) post immunization with either vehicle or Upadacitinib. To evaluate the severity of arthritis, paw swelling was evaluated with a water displacement plethysmograph every other day up to Day 17. On Day 17, all rats were exsanguinated by cardiac puncture under isolfuorane anesthesia. Left rear paws were scanned using a Micro-CT.Bone volume and density were determined in a 360μm vertical section encompassing the tarsal section of the paw. |
Dosage form | 0.1, 0.3, 1, 3, 10mg/kg; twice a day for 10 days; p.o. |
Applications | Upadacitinib administration improved synovial hypertrophy, inflammation, cartilage damage and bone erosion at the 3 and 10mg/kg dose groups. |
References: | |
| Cas No. | 1310726-60-3 | SDF | |
| Synonyms | ABT-494 | ||
| Canonical SMILES | O=C(N1C[C@@H](CC)[C@@H](C2=CN=C3C=NC(NC=C4)=C4N32)C1)NCC(F)(F)F | ||
| Formula | C17H19F3N6O | M.Wt | 380.37 |
| Solubility | DMSO : ≥ 22 mg/mL (57.84 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.629 mL | 13.1451 mL | 26.2902 mL |
| 5 mM | 525.8 μL | 2.629 mL | 5.258 mL |
| 10 mM | 262.9 μL | 1.3145 mL | 2.629 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 7 reference(s) in Google Scholar.)