| Size | Price | Stock | Qty |
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| Targets |
Tyk2-IN-7 targets the TYK2 JH2 (Janus homology 2) domain, which is the regulatory pseudokinase domain of tyrosine kinase 2 (TYK2). By binding to the JH2 domain with high affinity (IC50: 0.00053 microM; Ki.app: 0.00007 microM), the compound allosterically inhibits TYK2 signaling. Tyk2-IN-7 also inhibits TYK2/JAK1/JAK2 kinase domains. It offers a selective alternative to orthosteric inhibitors.
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| ln Vitro |
Tyk2-IN-7 demonstrates potent in vitro inhibition of TYK2 JH2 domain binding with IC50 of 0.00053 microM (530 pM) and Ki.app of 0.00007 microM (70 pM). The compound shows high selectivity for TYK2. It also inhibits TYK2/JAK1/JAK2 kinase domains. The compound is orally active. Purity is typically >99%. Tyk2-IN-7 provides robust inhibition in cellular assays.
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| ln Vivo |
In vivo, Tyk2-IN-7 provides robust inhibition in a mouse IL-12-induced IFNgamma pharmacodynamic model. It also shows efficacy in an IL-23 and IL-12-dependent mouse colitis model. The compound is orally active. These in vivo results demonstrate the compound's potential for treating TYK2-mediated inflammatory diseases. Tyk2-IN-7 shows good pharmacodynamic activity following oral administration.
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| Enzyme Assay |
In vitro enzyme binding assays for Tyk2-IN-7 typically employ recombinant TYK2 JH2 domain protein and measure binding affinity using surface plasmon resonance (SPR), fluorescence polarization, or similar techniques. The IC50 of 0.00053 microM and Ki.app of 0.00007 microM are determined from binding isotherms. Selectivity profiling against other kinases including JAK1 and JAK2 is performed. Assays are performed in appropriate buffer conditions.
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| Cell Assay |
Cellular assays for Tyk2-IN-7 involve treating TYK2-dependent cell lines with varying concentrations of the compound (typically 0.001-10 microM range) for 4-24 hours. Readouts include assessment of TYK2-mediated STAT phosphorylation by Western blotting, cytokine-induced signaling pathways, and downstream gene expression. IL-12-induced IFNgamma production is a key pharmacodynamic readout. IC50 values are determined from dose-response curves.
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| Animal Protocol |
In vivo animal studies for Tyk2-IN-7 employ mouse models including IL-12-induced IFNgamma pharmacodynamic models and IL-23/IL-12-dependent colitis models. Mice are administered Tyk2-IN-7 via oral gavage at various doses. Pharmacodynamic endpoints include measurement of IFNgamma levels, assessment of colitis severity, and evaluation of inflammatory markers. The compound shows robust inhibition in these models.
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| ADME/Pharmacokinetics |
Tyk2-IN-7 is orally active with favorable pharmacokinetic properties. Following oral administration, the compound achieves appropriate exposure for target engagement. PK parameters including half-life, Cmax, Tmax, and AUC are determined via LC-MS/MS analysis. The compound's oral bioavailability supports convenient dosing regimens. Molecular weight of 401.46 suggests favorable drug-like properties.
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| Toxicity/Toxicokinetics |
Toxicological data for Tyk2-IN-7 is limited to research-grade handling information. As a JAK family inhibitor, potential toxicities may include immunosuppression and other JAK-related effects. The compound shows a favorable profile in preclinical models. Standard safety precautions should be observed during handling including appropriate PPE and work in a fume hood. Comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
Tyk2-IN-7 (CAS# 1609391-90-3) is an orally active, selective TYK2 JH2 domain inhibitor. It provides a highly selective alternative to conventional TYK2 orthosteric inhibitors. The compound shows robust inhibition in mouse IL-12-induced IFNgamma pharmacodynamic models and efficacy in IL-23/IL-12-dependent colitis models. It is not approved for clinical use and is for research purposes only. The compound is typically stored at -20degC.
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| Molecular Formula |
C18H18N6O3S
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|---|---|
| Molecular Weight |
398.438921451569
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| Exact Mass |
401.134
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| CAS # |
1609391-90-3
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| PubChem CID |
138911330
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| Appearance |
Off-white to yellow solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
625
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N(C1C=CC=CC=1S(=O)(=O)C)C1C=C(NC2N=CC=CC=2)N=NC=1C(=O)NC([H])([H])[H]
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| InChi Key |
KUHISBZXQSKCLH-FIBGUPNXSA-N
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| InChi Code |
InChI=1S/C18H18N6O3S/c1-19-18(25)17-13(21-12-7-3-4-8-14(12)28(2,26)27)11-16(23-24-17)22-15-9-5-6-10-20-15/h3-11H,1-2H3,(H,19,25)(H2,20,21,22,23)/i1D3
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| Chemical Name |
4-(2-methylsulfonylanilino)-6-(pyridin-2-ylamino)-N-(trideuteriomethyl)pyridazine-3-carboxamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~249.09 mM)
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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 | 2.5098 mL | 12.5489 mL | 25.0979 mL | |
| 5 mM | 0.5020 mL | 2.5098 mL | 5.0196 mL | |
| 10 mM | 0.2510 mL | 1.2549 mL | 2.5098 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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