製品番号: HY-150101

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 番号: 1798578-61-6
分子式: C₃₄H₄₁FN₁₀O₂
分子量:640.75

保管条件:

Please store the product under the recommended conditions in the Certificate of Analysis.

LAS194046 構造式

CAS 番号: 1798578-61-6

価格（税別）

Amount: USD 0.00

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

生物活性
- 製品説明
- IC₅₀ & Target
- Cellular Effect
- 体外実験
- Parmacokinetics
- 体内実験
化学情報
純度とドキュメンテーション
参考文献
Calculators
Help & FAQs
関連分類
Bioz

生物活性

製品説明

IC₅₀ & Target

^[2]^[1]

JAK1

5.46 nM (IC₅₀)

JAK2

0.4 nM (IC₅₀)

JAK3

2.07 nM (IC₅₀)

IL-8

MMP-9

Tyk2

21.8 nM (IC₅₀)

JAK アイソフォーム固有の製品をすべて表示 :

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Cellular Effect

Cell Line	Type	Value	Description	References
Lymphocyte	IC50	16 nM	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.	31085698
Monocyte	IC50	26 nM	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.	31085698
Monocyte	IC50	37 nM	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.	31085698
Lymphocyte	IC50	24 nM	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.	31085698
Lymphocyte	IC50	220 nM	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.	31085698
CHO-K1	IC50	45 μM	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.	31085698
Ramos	IC50	17 nM	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.	Discovery-of-LAS194046-A-Potent-and-Selective-pan
CHO	IC50	45 μM	Cytotoxicity against Chinese Hamster Ovary (CHO) cells. Cytotoxicity against Chinese Hamster Ovary (CHO) cells.	Discovery-of-LAS194046-A-Potent-and-Selective-pan

体外実験

Innate ImmunityCytokines & ChemokinesOthers

Innate Immunity

Cytokines & Chemokines

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].

Others

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

Species	Dose	Route	T_1/2	F	CL	V_ss
Rat^[3]	0.3 mg/kg	i.t.	11.4 h	73 %	/	/
Rat^[3]	1 mg/kg	i.v.	13 h	/	147 mL/min/kg	124 L/kg

体内実験

Innate ImmunityCytokines & ChemokinesAdaptive Immunity

Innate Immunity

Cytokines & Chemokines

LAS194046 (0.3-1 mg/kg; i.t.; single dose 1 hour before ovalbumin challenge) reduces allergen-induced airway inflammation, late asthmatic response, and STAT phosphorylation in a rat asthma model, while 0.3 mg/kg significantly inhibits pSTAT⁶ phosphorylation^[2].

Adaptive Immunity

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.

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]
Dosage:

0.3 mg/kg; 1 mg/kg
Administration:

i.t.; single dose 1 hour before ovalbumin challenge
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.

Related Protocols :

化学情報

CAS 番号 1798578-61-6
分子量 640.75
分子式 C₃₄H₄₁FN₁₀O₂
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
輸送条件

Room temperature in continental US; may vary elsewhere.
保管条件

Please store the product under the recommended conditions in the Certificate of Analysis.

純度とドキュメンテーション

取扱説明書 (2659 KB)

参考文献

[1]. Milara J, et al. The pan-JAK inhibitor LAS194046 reduces neutrophil activation from severe asthma and COPD patients in vitro. Scientific reports. 2022 Mar 24;12(1):5132.

[2]. Calbet M, et al. Novel Inhaled Pan-JAK Inhibitor, LAS194046, Reduces Allergen-Induced Airway Inflammation, Late Asthmatic Response, and pSTAT Activation in Brown Norway Rats. The Journal of pharmacology and experimental therapeutics. 2019 Aug;370(2):137-147. [Content Brief]

[3]. Bach J, et al. Discovery of LAS194046: A Potent and Selective pan-Janus Kinase (JAK) Inhibitor with a Suitable Profile for Inhaled Administration[J]. Journal of Medicinal Chemistry, 2026, 69(16): 19601-19632.

Calculators

モル濃度計算機

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

濃度濃度

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分子量分子量

希釈計算機

濃度 _(開始) × 体積 _(開始) = 濃度 _(終了) × 体積 _(終了)

濃度 _(開始) 濃度 _(開始)

体積 _(開始) 体積 _(開始)

濃度 _(終了) 濃度 _(終了)

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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LAS194046

JAK アイソフォーム固有の製品をすべて表示

Interleukin Related アイソフォーム固有の製品をすべて表示

MMP アイソフォーム固有の製品をすべて表示

生物活性