JAK1/TYK2-IN-3
JAK1/TYK2-IN-3 is a potent, selective and orally active dual TYK2/JAK1 inhibitor with IC50 values of 6 and 37 nM, respectively. JAK1/TYK2-IN-3 also shows selectively relative to JAK2 (IC50=140 nM) and JAK3 (IC50=362 nM). JAK1/TYK2-IN-3 shows anti-inflammatory effect by regulating the expression of related TYK2/JAK1-regulated genes, as well as the formation of Th1, Th2, and Th17 cells.
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- CAS No.: 2734918-37-5
- Formule: C17H21F2N7O
- Masse moléculaire:377.39
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
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Help & FAQs
Activité biologique
Description
IC50 & Target
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Tyk2 6 nM (IC50) |
JAK1 37 nM (IC50) |
JAK2 140 nM (IC50) |
JAK3 362 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| H9c2 | IC50 |
13.4 μM
Compound: 48
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Cytotoxicity against rat H9C2 cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
Cytotoxicity against rat H9C2 cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
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[PMID: 35113547] |
| HUVEC | IC50 |
76.7 μM
Compound: 48
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Cytotoxicity against HUVEC cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
Cytotoxicity against HUVEC cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
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[PMID: 35113547] |
| L02 | IC50 |
146.9 μM
Compound: 48
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Cytotoxicity against human LO2 cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
Cytotoxicity against human LO2 cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
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[PMID: 35113547] |
In Vitro
JAK1/TYK2-IN-3 (compound 48) (10, 20, 30 mg/kg) shows anti-inflammatory effect by regulating the formation of Th1, Th2, Th17 cells[1].
JAK1/TYK2-IN-3 (10, 20, 30 mg/kg) inhibits the NF-κB signaling pathway by inhibits the JAK-STAT pathway, thereby reducing the inflammatory response in ulcerative colitis (UC) mice[1].
JAK1/TYK2-IN-3 (10, 20, 30 mg/kg) dose-dependently inhibits the mRNA expression of TNF-α, IL-1β, IL-12, IL-17A, IL-22, IFN-α, and IFN-β[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
JAK1/TYK2-IN-3 (5 mg/kg, p.o.) shows 23.7% oral bioavailability in rats[1].
Pharmacokinetic Parameters of JAK1/TYK2-IN-3 in male Sprague-Dawley rats[1].
| compd | dose(mg/kg) | Administration | Cmax(ng/mL) | Cl (Lh-1kg-1) | T1/2(h) | AUC0-t(ng·h/mL) | F (%) |
| 48 | 5 mg/kg | p.o. | 400.4±55.3 | 11.3±5.2 | 2.4±2.1 | 440.9±157.0 | 23.7 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:6-8 weeks, 270-325g male Sprague-Dawley rats[1]
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Dosage:5 mg/kg
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Administration:p.o.
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Result:Showed 23.7% oral bioavailability in rats.
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Animal Model:Six-eight week old male C57BL/6 mice, 20-22 g (2.5% dextran sulfate sodium (DSS)-induced acute UC mouse model)[1]
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Dosage:10, 20, 30 mg/kg
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Administration:p.o., twice a day, 12 days
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Result:Improved the infiltration of inflammatory factors and reduced the damage caused by DSS.
Chemical Information
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CAS No. 2734918-37-5
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Masse moléculaire 377.39
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Formule C17H21F2N7O
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SMILES
O=C1NCCC12CCN(C3=NC(NC4=CN(C(F)F)N=C4)=NC=C3C)CC2
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Naïve CD4+ T-cell subset differentiation/polarization
Naïve CD4+ T-cell subset differentiation/polarization is an in vitro assay in which purified naïve CD4+ T cells are activated through TCR and CD28 costimulation and cultured with defined cytokines and neutralizing antibodies to generate Th0, Th1, Th2, Th17, or induced Treg-like populations. Differentiation is detected by subset-associated cytokines and transcription factors: IFN-γ/T-bet for Th1, IL-4/GATA3 for Th2, IL-17A/RORγt for Th17, and Foxp3 for induced Treg cells. The assay readout is usually generated by intracellular cytokine staining after restimulation, transcription-factor staining by flow cytometry, ELISA of secreted cytokines, or gene-expression analysis. The result reflects cytokine-directed lineage commitment or polarization rather than antigen-specific immune protection by itself.
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JAK1/TYK2-IN-3 Related Classifications
HY-143885 Related Classifications
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