| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
The primary target of JAK3i is Janus kinase 3 (JAK3), a non-receptor tyrosine kinase that plays a critical role in cytokine receptor signaling in immune cells. JAK3 is essential for signaling through the common gamma chain (γc) cytokine receptors, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors. JAK3i is a highly selective, covalent JAK3 inhibitor that forms a covalent bond with a cysteine residue in the JAK3 kinase domain. This covalent binding mechanism provides sustained target inhibition and high selectivity (>3,000-fold) over JAK1, JAK2, and TYK2.
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| ln Vitro |
In vitro, JAK3i inhibits JAK3 kinase activity with an IC50 of 0.43 nM. It shows >3,000-fold selectivity over JAK1, JAK2, and TYK2. The compound forms covalent bonds with cysteines in JAK3 but not with closely related kinase domains in JAK1, JAK2, or TYK2. JAK3i reveals two distinct temporal waves of STAT5 phosphorylation and more potently targets the second wave, which is required for cell cycle progression and T cell proliferation. This selective targeting of the second wave of STAT5 phosphorylation may explain its potent anti-proliferative effects.
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| ln Vivo |
In vivo, JAK3i inhibits IL-2-driven T cell growth and proliferation. By covalently inhibiting JAK3, the compound suppresses cytokine signaling and T cell activation in vivo. Its high selectivity for JAK3 over other JAK family members suggests a favorable therapeutic window. The compound has potential in autoimmune disease research. However, specific in vivo efficacy data from animal models is not detailed in the available sources.
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| Enzyme Assay |
For JAK3 inhibitors, standard cell-free assays involve measuring the kinase activity of recombinant JAK3 enzyme using peptide substrates. The compound is incubated with the enzyme, ATP, and substrate, and phosphorylation is detected by radioactive or fluorescent methods to determine IC50 values. Covalent binding can be confirmed by mass spectrometry or washout experiments to demonstrate irreversible inhibition.
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| Cell Assay |
For JAK3 inhibitors, standard cellular assays involve treatment of immune cells (e.g., T cells, NK cells) with the test compound in the presence of IL-2 or other γc cytokines. JAK3/STAT5 signaling is assessed by measuring STAT5 phosphorylation by western blot or flow cytometry. T cell proliferation is measured by [³H]-thymidine incorporation or CFSE dilution. Cell viability is assessed using MTT or CellTiter-Glo assays.
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| Animal Protocol |
For in vivo evaluation of JAK3 inhibitors, standard animal models include autoimmune disease models (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis) and T cell-mediated inflammatory models. The compound is typically administered orally or intraperitoneally for 2-4 weeks. T cell activation, cytokine levels, and disease severity are assessed. JAK3i inhibits IL-2-driven T cell growth/proliferation in vivo.
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| ADME/Pharmacokinetics |
JAK3i has a molecular weight of 354.34 and formula C18H15FN4O3. The chemical name is Ethyl 4-(5-acrylamido-2-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability and oral bioavailability. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for JAK3i is not provided in the available sources. As a covalent inhibitor, JAK3i may have potential for off-target reactivity that would need to be carefully evaluated. However, its high selectivity (>3,000-fold) for JAK3 over other JAK family members suggests a favorable specificity profile. Standard preclinical toxicology would be required for therapeutic development. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
JAK3i is a highly selective, potent, covalent JAK3 kinase inhibitor with an IC50 of 0.43 nM. It shows >3,000-fold selectivity over JAK1, JAK2, and TYK2. JAK3i forms covalent bonds with cysteines in JAK3 but not with closely related kinase domains. The compound reveals two distinct temporal waves of STAT5 phosphorylation and more potently targets the second wave, which is required for cell cycle progression and T cell proliferation. No regulatory approval has been identified.
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| Molecular Formula |
C18H15FN4O3
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|---|---|
| Molecular Weight |
354.335107088089
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| Exact Mass |
354.112
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| CAS # |
1918238-72-8
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| PubChem CID |
118705186
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
547
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=CNC2=NC=NC(=C12)C3=C(C=CC(=C3)NC(=O)C=C)F
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| InChi Key |
KNLROUBMVYVLGX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H15FN4O3/c1-3-14(24)23-10-5-6-13(19)11(7-10)16-15-12(18(25)26-4-2)8-20-17(15)22-9-21-16/h3,5-9H,1,4H2,2H3,(H,23,24)(H,20,21,22)
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| Chemical Name |
ethyl 4-[2-fluoro-5-(prop-2-enoylamino)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate
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| Synonyms |
JAK-3i; JAK 3i; JAK3i
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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 | 2.8221 mL | 14.1107 mL | 28.2215 mL | |
| 5 mM | 0.5644 mL | 2.8221 mL | 5.6443 mL | |
| 10 mM | 0.2822 mL | 1.4111 mL | 2.8221 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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