| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
JAK3; less active diastereomer/enantiomer of Tofacitinib
(3R,4S)-Tofacitinib targets Janus kinase 3 (JAK3) with an IC₅0 of 1 nM. It shows 20- to 100-fold less potency against JAK2 and JAK1 compared to JAK3. As a JAK inhibitor, it interferes with the JAK-STAT signaling pathway, which is involved in immune cell activation, proliferation, and cytokine signaling. |
|---|---|
| ln Vitro |
(3R,4S)-Tofacitinib is an impurity of Tofacitinib and is a less active diastereomer of Tofacitinib.
In vitro, (3R,4S)-Tofacitinib is significantly less active than the (3S,4R) enantiomer of Tofacitinib. While the active enantiomer potently inhibits JAK3-mediated signaling and T-cell proliferation, the (3R,4S) enantiomer shows markedly reduced inhibitory activity, providing a valuable negative control for studying JAK3-dependent effects in cellular systems. |
| ln Vivo |
In vivo activity data for the (3R,4S) enantiomer specifically are limited. Tofacitinib (the racemic or active enantiomer) is highly efficacious in treating rheumatoid arthritis and other autoimmune conditions. The (3R,4S) enantiomer is not used therapeutically but serves as a research tool to distinguish enantiomer-specific effects in preclinical models.
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| Enzyme Assay |
In vitro enzyme binding assays for JAK inhibitors are performed using purified recombinant JAK3 kinase domains. The compound is incubated with the kinase, ATP, and a peptide substrate in a kinase buffer. Phosphorylated substrate is detected using luminescence-based (e.g., ADP-Glo) or fluorescence-based methods. IC₅0 values are calculated from dose-response curves generated with serial dilutions of the compound (0.01-1000 nM).
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| Cell Assay |
Cellular assays for (3R,4S)-Tofacitinib are conducted using JAK3-dependent cell lines such as IL-2-stimulated T-cells or CTLL-2 cells. Cells are treated with serial dilutions of the compound for 48-72 hours. Cell proliferation is measured by BrdU incorporation or MTT assay. STAT5 phosphorylation, a downstream marker of JAK3 activity, is assessed by flow cytometry or Western blot. The (3R,4S) enantiomer serves as a negative control in these assays.
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| Animal Protocol |
In vivo studies for enantiomer comparison typically involve administering the (3R,4S) enantiomer and the active enantiomer to rodent models of autoimmune disease (e.g., collagen-induced arthritis). Standard endpoints include assessment of clinical disease scores, joint histopathology, and inflammatory cytokine levels. The (3R,4S) enantiomer is expected to show minimal efficacy compared to the active enantiomer.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of (3R,4S)-Tofacitinib are expected to be similar to those of Tofacitinib due to identical physicochemical properties. Tofacitinib has good oral bioavailability, moderate plasma protein binding, and a half-life of approximately 3 hours. It is metabolized primarily by CYP3A4 and excreted via both renal and hepatic routes. The compound is formulated for oral administration.
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| Toxicity/Toxicokinetics |
Toxicological data specific to the (3R,4S) enantiomer are not extensively characterized. Tofacitinib has been extensively studied in clinical trials and shows a manageable safety profile with adverse effects including infections, gastrointestinal symptoms, and lipid profile changes. The (3R,4S) enantiomer, being less pharmacologically active, is expected to have a different toxicity profile.
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| References |
[1]. https://pubchem.ncbi.nlm.nih.gov/compound/25180101
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| Additional Infomation |
(3r,4s)-Tofacitinib is an N-acylpiperidine.
(3R,4S)-Tofacitinib is a research-use compound not approved for clinical therapeutic applications. It is used as a negative control and tool compound in studies investigating JAK3 signaling, the stereospecificity of JAK inhibitors, and the mechanisms of action of Tofacitinib. The compound is valuable for understanding the contribution of enantiomer-specific effects in JAK3-mediated biological processes. |
| Molecular Formula |
C16H20N6O
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|---|---|
| Molecular Weight |
312.3696
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| Exact Mass |
312.169
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| Elemental Analysis |
C, 61.52; H, 6.45; N, 26.90; O, 5.12
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| CAS # |
1092578-46-5
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| Related CAS # |
Tofacitinib;477600-75-2;Tofacitinib citrate;540737-29-9;(3S,4S)-Tofacitinib;1092578-47-6;(3S,4R)-Tofacitinib;1092578-48-7
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| PubChem CID |
25180101
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
585.8±50.0 °C at 760 mmHg
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| Flash Point |
308.1±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
0.93
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
488
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]1CCN(C[C@@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N
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| InChi Key |
UJLAWZDWDVHWOW-AAEUAGOBSA-N
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| InChi Code |
InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13-/m0/s1
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| Chemical Name |
3-[(3R,4S)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile
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| Synonyms |
Tofacitinib Impurity A; (3R,4S)-Tofacitinib; 1092578-46-5; 3-((3R,4S)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile; B64WR5WNB7; Epitofacitinib, (3R,4S)-; CHEMBL457871; 3-[(3R,4S)-4-METHYL-3-[METHYL(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]PIPERIDIN-1-YL]-3-OXOPROPANENITRILE; (3R,4S)-(+)-Tofacitinib isomer;
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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) |
DMSO : ~100 mg/mL (~320.13 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2013 mL | 16.0067 mL | 32.0133 mL | |
| 5 mM | 0.6403 mL | 3.2013 mL | 6.4027 mL | |
| 10 mM | 0.3201 mL | 1.6007 mL | 3.2013 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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