| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
Tyk2-IN-5 targets tyrosine kinase 2 (Tyk2), a member of the Janus kinase (JAK) family involved in cytokine signaling. The compound binds to the JH2 (pseudokinase) domain of Tyk2, stabilizing the regulatory domain and inhibiting Tyk2-mediated signaling, including IFNalpha and IFNgamma pathways.
|
|---|---|
| ln Vitro |
Tyk2-IN-5 exhibits Jak1-3-dependent cellular activity with an IC50 of >12.5 μM and inhibits Jak1-3 with an IC50 value of >2 μM [1].
In vitro, Tyk2-IN-5 inhibits Jak1-3 with lower potency than Tyk2. The compound shows a Ki of 0.086 nM for Tyk2 JH2 and an IC₅0 of 25 nM for IFNalpha. It selectively inhibits Tyk2-mediated signaling over other JAK family members. |
| ln Vivo |
In adjuvant arthritis models, Tyk2-IN-5 (5, 10 mg/kg; face; twice daily for 20 days) exhibits high efficacy [1]. In a dose-dependent manner, Tyk2-IN-5 (1, 10 mg/kg; basalt) suppresses the generation of IFNγ produced by IL-12/IL-18 [1]. One dose of Tyk2-IN-5 (10 mg/kg; dam) has been recorded in the
In vivo, Tyk2-IN-5 efficiently inhibits the production of IFNgamma in a pharmacodynamic rat model and is fully efficacious in a rat model of arthritis. The compound is orally active and demonstrates robust efficacy in preclinical models of autoimmune and inflammatory diseases. |
| Enzyme Assay |
For in vitro enzyme binding assays, Tyk2-IN-5 is evaluated using recombinant Tyk2 JH2 domain in binding or kinase activity assays. The compound is incubated with the enzyme and a substrate, and inhibitory activity is measured. Ki values are calculated from binding kinetics or dose-response curves.
|
| Cell Assay |
For in vitro cellular assays, Tyk2-IN-5 is dissolved in DMSO and applied to cells stimulated with IFNalpha or other cytokines. Tyk2-mediated signaling (e.g., STAT phosphorylation) is assessed using Western blotting or phospho-flow cytometry. Inhibition of IFNalpha-induced gene expression is also measured.
|
| Animal Protocol |
Animal/Disease Models: Lewis male rat (IL-12/IL-18 induced) [1].
Doses: 1, 10 mg/kg Route of Administration: Oral; Single Experimental Results:IL-12/IL-18-induced IFNγ production was inhibited by 45% and 77% at doses of 1 and 10 mg/kg, respectively. Animal/Disease Models: Lewis male rat, mouse [1]. Doses: 10 mg/kg Route of Administration: po (po (oral gavage)) Single Experimental Results:1.19 pharmacokinetic/PK/PK parameters of Tyk2-IN-5 in mice and rats [1]. PO (10 mg/kg) Mouse Rat Cmax (μM) 15 9.4 AUC0-24 (μM·h) 19 57 CL (mL/min/kg) 16 7.8 F (%) 86 114 In vivo animal studies with Tyk2-IN-5 typically involve oral administration in rat models of arthritis or other autoimmune diseases. Common endpoints include clinical score, paw swelling, inflammatory cytokine levels (e.g., IFNgamma), and histopathological analysis of joint tissues. |
| ADME/Pharmacokinetics |
Pharmacokinetic data indicate that Tyk2-IN-5 is orally active and bioavailable. The compound has a molecular weight of 434.43 and molecular formula C21H1₉FN₈O2. Detailed PK parameters (e.g., Cmax, AUC, t1/2) are available in the primary literature.
|
| Toxicity/Toxicokinetics |
Toxicology data for Tyk2-IN-5 are limited to preclinical observations. The compound has demonstrated efficacy in rat models of arthritis with acceptable tolerability. As a JAK family inhibitor, potential off-target effects on other JAK isoforms should be considered. Not approved for human use.
|
| References | |
| Additional Infomation |
Tyk2-IN-5 (CAS#: 1797432-62-2) has the molecular formula C21H1₉FN₈O2 and molecular weight 434.43. The chemical name is N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)-6-({2-oxo-2H-[1,2'-bipyridin]-3-yl}amino)imidazo[1,2-b]pyridazine-3-carboxamide. It is a research reagent only.
|
| Molecular Formula |
C21H19FN8O2
|
|---|---|
| Molecular Weight |
434.426366090775
|
| Exact Mass |
434.161
|
| CAS # |
1797432-62-2
|
| PubChem CID |
91809175
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
1.9
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
807
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
F[C@H]1C[C@H]1NC(C1=CN=C2C(=CC(NC3=CC=CN(C4C=CC=CN=4)C3=O)=NN12)NC)=O
|
| InChi Key |
YITUGUNLCGLOII-GXTWGEPZSA-N
|
| InChi Code |
InChI=1S/C21H19FN8O2/c1-23-15-10-17(26-13-5-4-8-29(21(13)32)18-6-2-3-7-24-18)28-30-16(11-25-19(15)30)20(31)27-14-9-12(14)22/h2-8,10-12,14,23H,9H2,1H3,(H,26,28)(H,27,31)/t12-,14+/m0/s1
|
| Chemical Name |
N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)-6-[(2-oxo-1-pyridin-2-ylpyridin-3-yl)amino]imidazo[1,2-b]pyridazine-3-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~43.33 mg/mL (~99.74 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (5.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3019 mL | 11.5093 mL | 23.0187 mL | |
| 5 mM | 0.4604 mL | 2.3019 mL | 4.6037 mL | |
| 10 mM | 0.2302 mL | 1.1509 mL | 2.3019 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
