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Purity: ≥98%
JAK3-IN-6 is a novel potent, selective, and irreversible inhibitor of Janus Associated Kinase 3 (JAK3) with anti-inflammatory effects. It inhibits JAK3 with an IC50 of 0.15 nM. JAK3-IN-6 was 4300-fold selective for JAK3 over JAK1 in enzyme assays, 67-fold [interleukin (IL)-2 versus IL-6] or 140-fold [IL-2 versus erythropoietin or granulocyte-macrophage colony-stimulating factor (GMCSF)] selective in cellular reporter assays and >35-fold selective in human peripheral blood mononuclear cell assays (IL-7 versus IL-6 or GMCSF). In vivo, selective JAK3 inhibition was sufficient to block the development of inflammation in a rat model of rheumatoid arthritis, while sparing hematopoiesis.
ln Vitro |
JAK3-IN-6 (Compound 2) is a powerful JAK3 inhibitor with a concentration of 0.15 nM. In an enzymatic assay, it demonstrates a 4300-fold greater selectivity for JAK3 than JAK1, meaning that it is 67-fold (IL-2 vs. IL-6) or 140-fold (IL-2 vs. EPO or GMCSF) selective in cell reporter gene assays and >35-fold (IL-7 vs. IL-6 or GMCSF) in human PBMC assays. In order to ascertain whether there is an additive or synergistic effect of synergy, JAK3-IN-6 was cross-titrated with JAK1 selective inhibitor 3 (JAK1: 0.96 nM, JAK2: 14 nM, JAK3: >1500 nM, TYK2: 10 nM). This cross-titration was irreversible. shows that the predicted pSTAT5 inhibition levels based on the addition of JAK1 and JAK3 inhibition are very close to the measured effects of cross-titration of each compound, indicating that inhibition of JAK1 and JAK3 is Blocking STAT5 phosphorylation has additive but not synergistic effects. Inhibits the JAK1 and JAK3 enzymes that inhibit IL-7 signaling in CD3+, CD4+ PBMC. Furthermore, JAK1 or JAK3 inhibition on its own is adequate to totally block pSTAT5 [2].
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References |
[1]. ARYL SULFONOHYDRAZIDES. WO2017027400A1.
[2]. Elwood F, et al. Evaluation of JAK3 Biology in Autoimmune Disease Using a Highly Selective, Irreversible JAK3 Inhibitor. J Pharmacol Exp Ther. 2017 May;361(2):229-244. |
Molecular Formula |
C19H18N4O3
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Molecular Weight |
350.38
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CAS # |
1443235-95-7
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O=C(C1=CNC2=NC=NC(C3=CC=CC(NC(C(C)=C)=O)=C3)=C21)OCC
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Chemical Name |
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Synonyms |
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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 |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (6.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (6.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.8540 mL | 14.2702 mL | 28.5404 mL | |
5 mM | 0.5708 mL | 2.8540 mL | 5.7081 mL | |
10 mM | 0.2854 mL | 1.4270 mL | 2.8540 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.
Predicted cellular potency of compound 1 confirmed by potency in single isozyme cellular assay.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |
Potent, selective irreversible JAK3 inhibitor 2. (A) Compound 2 structure. (B) Confirmation of covalent binding by X-ray crystallography. (C) Waterfall plot demonstrating selectivity of compound 2 against the kinome. td> |
Fractional activity remaining and relative affinity (kinact/KI) determination.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |
Multiparameter flow cytometry in human whole blood demonstrates pSTAT signature of compound 2 specific to JAK3 signaling.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |
No synergy observed in pSTAT5 PBMC assay in response to IL-7 with cross-titrated JAK1 and JAK3 inhibitors.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |
Prophylactic inhibition of JAK3 in a rat CIA model blocks paw swelling and joint degradation.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |
Therapeutic inhibition of JAK3 in a rat CIA model partially blocks paw swelling and joint degradation.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |
Inhibition of leukocyte proliferation, but not erythrocyte proliferation, by compound 2 in rats.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |
Ex vivo pSTAT inhibition by compound 2 in rat whole blood. pSTAT signal in whole blood obtained from rats dosed with 300 mg/kg of compound 2 and stimulated with cytokines ex vivo.J Pharmacol Exp Ther.2017 May;361(2):229-244. td> |