JAK2/TYK2-IN-1 is a dual JAK2/TYK2 inhibitor with anti-inflammatory activity. Exhibits IC50 of 9 and 157 nM for TYK2 and JAK2, respectively.
Physicochemical Properties
| Molecular Formula | C19H13F4N7O2S |
| Molecular Weight | 479.410835027695 |
| Exact Mass | 479.078 |
| CAS # | 2613434-12-9 |
| PubChem CID | 155817516 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 33 |
| Complexity | 845 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | CGDRNYQWTORWBT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C19H13F4N7O2S/c20-15-10-25-18(28-17(15)13-9-26-29(11-13)6-1-5-24)27-14-2-3-16-12(8-14)4-7-30(16)33(31,32)19(21,22)23/h2-4,7-11H,1,6H2,(H,25,27,28) |
| Chemical Name | 3-[4-[5-fluoro-2-[[1-(trifluoromethylsulfonyl)indol-5-yl]amino]pyrimidin-4-yl]pyrazol-1-yl]propanenitrile |
| 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) |
Biological Activity
| ln Vitro | JAK2/TYK2-IN-2 (compound 14l; 0-10000 nM) suppresses STAT phosphorylation in vitro [1]. |
| ln Vivo | JAK2/TYK2-IN-2 (10 and 20 mg/kg; orally; twice daily for 6 days) displays anti-inflammatory effects in a dose-dependent manner [1]. JAK2/TYK2-IN-2 (5, 20 mg/kg; oral dose; twice daily for 12 days) results in low oral bioavailability [1]. Pharmacokinetic parameters of JAK1/TYK2-IN-2 in male Sprague-Dawley rats [1] PK parameter iv PK parameter po AUC(0-t) (μg/L*h) 29.00 AUC(0-t) (μg/L* h) 13.89 MRT(0-t) (h) 4.98 MRT(0-t) (h) 2.76 t1/2 (h) 5.95 t1/2 (h) 3.64 Cl (L/min/kg) 1.58 Cl (L/ min/kg) 20.55 Vss (L/kg) 985.41 Vss (L/kg) 6564.28 Cmax (μg/L) 48.55 Cmax (μg/L) 8.00 Tmax (h) 1.00 F 11.96% |
| Cell Assay |
Western Blot Analysis[1] Cell Types: TF-1, H9, TF-1, THP-1 Cell Tested Concentrations: 0-10000 nM Incubation Duration: Experimental Results: After stimulation with IL-6 and IFN-α at concentrations from 100 to 100 JAK2/TYK2-IN-2 diminished JAK1/JAK2/TYK2 and JAK1/TYK2-dependent signaling in a dose-dependent manner at 5000 nM and Dramatically diminished IFN-α-induced phosphorylation at 10 000 nM. |
| Animal Protocol |
Animal/Disease Models: 6 -8 weeks old male C57BL/6 mice, 20-22 g (acute mouse colitis model) [1] Doses: 10, 20 mg/kg (dissolved in 5% EtOH, 1% propylene glycol, 0.5% Tween 80 and 92.5% normal saline) Route of Administration: Orally, twice a day, for 6 days. Experimental Results: It has anti-inflammatory activity and has a good therapeutic effect on inflammatory bowel disease (IBD) in a dose-dependent manner. |
| References |
[1]. Discovery of 3-(4-(2-((1H-Indol-5-yl) amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl) propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease. J Med Chem. 2021; 64(4):1966-1988. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0859 mL | 10.4295 mL | 20.8590 mL | |
| 5 mM | 0.4172 mL | 2.0859 mL | 4.1718 mL | |
| 10 mM | 0.2086 mL | 1.0429 mL | 2.0859 mL |