LAS194046
LAS194046 is a selective pan-JAK inhibitor, with an IC50 of 5.46 nM against JAK1, 0.4 nM against JAK2, and 2.07 nM against JAK3. LAS194046 reduces the levels of IL-8 and MMP-9. LAS194046 enhances the activation of glucocorticoid response elements by Fluticasone propionate. LAS194046 inhibits T2-type allergic pulmonary inflammation, allergen-induced airway inflammation, and late-phase asthmatic responses in rats. LAS194046 can be used in research related to non-T2 severe asthma, chronic obstructive pulmonary disease, and asthma.
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- CAS No.: 1798578-61-6
- Formule: C34H41FN10O2
- Masse moléculaire:640.75
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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
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- Références
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Activité biologique
Description
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JAK1 5.46 nM (IC50) |
JAK2 0.4 nM (IC50) |
JAK3 2.07 nM (IC50) |
IL-8 |
MMP-9 |
Tyk2 21.8 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| Lymphocyte | IC50 |
16 nM
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Inhibition of JAK1/JAK3-dependent IL-4-induced pSTAT6 in human peripheral blood mononuclear cell lymphocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
Inhibition of JAK1/JAK3-dependent IL-4-induced pSTAT6 in human peripheral blood mononuclear cell lymphocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
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31085698 |
| Monocyte | IC50 |
26 nM
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Inhibition of JAK1/JAK3-dependent IL-4-induced pSTAT6 in human peripheral blood mononuclear cell monocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
Inhibition of JAK1/JAK3-dependent IL-4-induced pSTAT6 in human peripheral blood mononuclear cell monocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
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31085698 |
| Monocyte | IC50 |
37 nM
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Inhibition of JAK2/JAK2-dependent GM-CSF-induced pSTAT5 in human peripheral blood mononuclear cell monocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
Inhibition of JAK2/JAK2-dependent GM-CSF-induced pSTAT5 in human peripheral blood mononuclear cell monocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
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31085698 |
| Lymphocyte | IC50 |
24 nM
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Inhibition of JAK1/TYK2-dependent IFN-α-induced pSTAT1 in human peripheral blood mononuclear cell lymphocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
Inhibition of JAK1/TYK2-dependent IFN-α-induced pSTAT1 in human peripheral blood mononuclear cell lymphocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
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31085698 |
| Lymphocyte | IC50 |
220 nM
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Inhibition of JAK2/TYK2-dependent IL-12-induced pSTAT4 in human peripheral blood mononuclear cell lymphocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
Inhibition of JAK2/TYK2-dependent IL-12-induced pSTAT4 in human peripheral blood mononuclear cell lymphocytes assessed by flow cytometry following 30 min pre-incubation with LAS194046 and 30 min cytokine activation.
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31085698 |
| CHO-K1 | IC50 |
45 μM
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Cytotoxicity against CHO-K1 cells assessed as reduction in cell viability incubated for 24 hrs by ATP luminescence using the ATPLite assay.
Cytotoxicity against CHO-K1 cells assessed as reduction in cell viability incubated for 24 hrs by ATP luminescence using the ATPLite assay.
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31085698 |
| Ramos | IC50 |
17 nM
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Inhibition of IL-4-induced STAT-6 phosphorylation (JAK1/3 pathway) in human Ramos cells.
Inhibition of IL-4-induced STAT-6 phosphorylation (JAK1/3 pathway) in human Ramos cells.
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Discovery-of-LAS194046-A-Potent-and-Selective-pan |
| CHO | IC50 |
45 μM
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Cytotoxicity against Chinese Hamster Ovary (CHO) cells.
Cytotoxicity against Chinese Hamster Ovary (CHO) cells.
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Discovery-of-LAS194046-A-Potent-and-Selective-pan |
In Vitro
LAS194046 (0.01 nM-1 µM; 1 h pre-incubation; 6 h CSE stimulation) concentration-dependently inhibits CSE-induced IL-8 and MMP-9 release in sputum neutrophils from severe COPD patients, with maximal inhibition of 57.27% for IL-8 and 74.34% for MMP-9[1].
LAS194046 (0.01 nM-1 µM) potentiates glucocorticoid response element activation in Beas2B bronchial epithelial cells when combined with a fixed 0.1 nM concentration of futicasone propionate[1].
LAS194046 (30 min (JAK1, JAK2, JAK3); 15 min (TYK2)) is a potent pan-JAK inhibitor of recombinant human JAK1, JAK2, and JAK3 kinases, with weaker activity against TYK2, displaying IC50 values of 5.46 nM, 0.4 nM, 2.07 nM, and 21.8 nM, respectively[2].
LAS194046 (30 min pre-incubation; 30 min cytokine activation) inhibits multiple JAK/STAT signaling pathways in human PBMCs, with potent activity against JAK1/JAK3, JAK1/TYK2, and JAK2/JAK2-dependent pathways (IC50 values 16-37 nM) and weaker activity against JAK2/TYK2-dependent signaling (IC50 = 220 nM)[2].
LAS194046 (24 h) exhibits low cytotoxicity in CHO-K1 cells, with an IC50 of 45 μM, well above concentrations required for JAK inhibition[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
LAS194046 (intratracheal) reduces allergen-induced airway inflammation and late asthmatic response in an ovalbumin-induced asthma model in Brown Norway rats via intratracheal administration, with sustained lung exposure and minimal systemic exposure[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Brown Norway (male, 150-170 g, intraperitoneally sensitized with ovalbumin + Imject Alum adjuvant on days 0, 14, 21; challenged with 1% ovalbumin aerosol on day 28)[2]
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Dosage:0.3 mg/kg; 1 mg/kg
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Administration:i.t.; single dose 1 hour before ovalbumin challenge
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Result:Inhibited eosinophil and neutrophil infiltration in BALF by 64% and 63%, respectively, and inhibited the late asthmatic response by 61% at 1 mg/kg.
Did not significantly inhibit inflammatory cell infiltration or late asthmatic response at 0.3 mg/kg.
Inhibited ovalbumin-induced pSTAT3 phosphorylation in lung homogenates by 50%, pSTAT1 phosphorylation by 79%, and pSTAT6 phosphorylation by 91% at 1 mg/kg.
Significantly inhibited ovalbumin-induced pSTAT6 phosphorylation by 80% at 0.3 mg/kg.
Chemical Information
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CAS No. 1798578-61-6
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Masse moléculaire 640.75
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Formule C34H41FN10O2
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SMILES
FC1=C(N=C(C2=C3N(C=CC=C3)N=C2)N=C1N4CCN(CC4)CC5=CC=C(C=C5)OCCN(C)C)N[C@H]6CN(CCC6)C(CC#N)=O
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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.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LAS194046 Related Classifications
HY-150101 Related Classifications
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