2. JAK/STAT Signaling Stem Cell/Wnt Immunology/Inflammation
  3. STAT Interleukin Related IFNAR
  4. QL-1200186

QL-1200186 is a selective, orally active, allosteric inhibitor targeting the tyrosine kinase TYK2 pseudokinase domain JH2 (IC50=0.06 nM, TYK2 JH2), with 164-fold selectivity over TYK1 JH2 (IC50=9.85 nM，TYK1 JH2). QL-1200186 first stabilizes the TYK2 JH2 conformation, inhibits the activity of the JH1 catalytic domain, and blocks the IFNα, IL-12/IL-23-mediated JAK-STAT signaling pathway. QL-1200186 can inhibit the production of Th1/Th17 cell-related cytokines (such as IFNγ, IL-23), reduce immune cell activation, and has no significant effect on JAK1/2/3 kinase activity. QL-1200186 can significantly improve skin inflammation in the Imiquimod (HY-B0180)-induced psoriasis mouse model and reduce the Psoriasis Area and Severity Index (PASI) score. QL-1200186 can be used in the study of autoimmune diseases such as psoriasis and systemic lupus erythematosus (SLE).

For research use only. We do not sell to patients.

QL-1200186 Chemical Structure

QL-1200186 Chemical Structure

CAS No. : 2848664-42-4

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Customer Review

Based on 1 publication(s) in Google Scholar

QL-1200186 Related Antibodies

Top Publications Citing Use of Products

View All STAT Isoform Specific Products:

View All Isoforms
STAT3 STAT5 STAT6 STAT1

View All Interleukin Related Isoform Specific Products:

View All Isoforms
IL-1 IL-2 IL-3 IL-4 IL-5 IL-6 IL-8 IL-10 IL-12 IL-13 IL-15 IL-17 IL-23 IL-7 IL-33 IL-22

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

QL-1200186 is a selective, orally active, allosteric inhibitor targeting the tyrosine kinase TYK2 pseudokinase domain JH2 (IC50=0.06 nM, TYK2 JH2), with 164-fold selectivity over TYK1 JH2 (IC50=9.85 nM，TYK1 JH2). QL-1200186 first stabilizes the TYK2 JH2 conformation, inhibits the activity of the JH1 catalytic domain, and blocks the IFNα, IL-12/IL-23-mediated JAK-STAT signaling pathway. QL-1200186 can inhibit the production of Th1/Th17 cell-related cytokines (such as IFNγ, IL-23), reduce immune cell activation, and has no significant effect on JAK1/2/3 kinase activity. QL-1200186 can significantly improve skin inflammation in the Imiquimod (HY-B0180)-induced psoriasis mouse model and reduce the Psoriasis Area and Severity Index (PASI) score. QL-1200186 can be used in the study of autoimmune diseases such as psoriasis and systemic lupus erythematosus (SLE)[1].

IC50 & Target

IL-12

 

IL-23

 

STAT1

 

STAT3

 

STAT5

 

In Vitro

QL-1200186 (1-10 μM; 30 min+15 min) inhibits IFNα-induced STAT1 phosphorylation (pSTAT1) in CD3+ T cells with an IC50 of 1.61 nM; in NK-92 cells and Th17 cells, the IC50s for IL-12-induced IFN-γ expression and IL-23-induced pSTAT3 are 32.48 nM and 1.026 nM, respectively[1].
QL-1200186 (1-10 μM; 48 h) inhibits IFNα-induced pSTAT5 in human PBMCs with an IC50 of 7.26 nM[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

QL-1200186 Related Antibodies

Western Blot Analysis[1]

Cell Line: HEK293 cells engineered to express human TYK2
Concentration: 0.001, 0.01, 0.1, 1, 10 μM
Incubation Time: 1 h
Result: Dose-dependently inhibited TYK2 autophosphorylation with an IC50 of 0.06 nM.
Reduced phosphorylation of TYK2 and downstream STAT proteins.
No significant inhibition of JAK1/2/3 was observed at concentrations up to 10 μM.
Parmacokinetics[1]
Species Dose Route Indicator value
Mice 1 mg/kg i.v. CL 11.6 mL/min/kg
Mice 10 mg/kg p.o. Cmax 3543 ng/mL
Mice 1 mg/kg i.v. Vss 0.843 L/kg
Mice 10 mg/kg p.o. AUC 20320 ng·h/mL
Mice 1 mg/kg i.v. MRT0-∞ 1.22 hr
Mice 10 mg/kg p.o. T1/2 2.73 hr
Mice 1 mg/kg i.v. AUC 1482 ng·h/mL
Mice 10 mg/kg p.o. MRT0-∞ 4.34 hr
Mice 1 mg/kg i.v. T1/2 1.45 hr
Mice 10 mg/kg p.o. F 137 %
In Vivo

QL-1200186 (1-10 mg/kg; oral; once daily; 3 days) inhibits serum IFNγ levels in a dose-dependent manner in an IL-12/IL-18-induced mouse inflammation model, with the highest inhibition rate reaching 97.8%[1].
QL-1200186 (5-30 mg/kg; oral; twice daily; 7 dayss) significantly reduces PASI scores and improves skin erythema, scaling and thickening in an Imiquimod (HY-B0180)-induced mouse psoriasis model, with skin thickness reduced by 49.7% in the 30 mg/kg group[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male BALB/c mice (18-20 g, 6-8 weeks) with Imiquimod-induced psoriasis-like dermatitis[1]
Dosage: 5, 10, 30 mg/kg
Administration: Oral gavage, twice daily for 7 days, concurrent with daily Imiquimod application (daily topical dose of 62.5  mg of 5% Imiquimod cream)
Result: Significantly lowered PASI scores in treatment groups compared to vehicle control.
Showed a 49.7% reduction in skin thickness, with decreased epidermal hyperplasia and immune cell infiltration observed by histopathology, at 30 mg/kg group.
Plasma drug concentrations correlated with therapeutic efficacy.
Molecular Weight

485.54

Formula

C26H27N7O3
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

COC(C(C(C=C1)=NN1C)=CC(CCOCC2=NC3=CC=C2)=C4)=C4NC(C=C(N3)N=C5)=C5C(NC)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (205.96 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.0596 mL 10.2978 mL 20.5956 mL
5 mM 0.4119 mL 2.0596 mL 4.1191 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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  • Dilution Calculator

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

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

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C2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.0596 mL 10.2978 mL 20.5956 mL 51.4891 mL
5 mM 0.4119 mL 2.0596 mL 4.1191 mL 10.2978 mL
10 mM 0.2060 mL 1.0298 mL 2.0596 mL 5.1489 mL
15 mM 0.1373 mL 0.6865 mL 1.3730 mL 3.4326 mL
20 mM 0.1030 mL 0.5149 mL 1.0298 mL 2.5745 mL
25 mM 0.0824 mL 0.4119 mL 0.8238 mL 2.0596 mL
30 mM 0.0687 mL 0.3433 mL 0.6865 mL 1.7163 mL
40 mM 0.0515 mL 0.2574 mL 0.5149 mL 1.2872 mL
50 mM 0.0412 mL 0.2060 mL 0.4119 mL 1.0298 mL
60 mM 0.0343 mL 0.1716 mL 0.3433 mL 0.8582 mL
80 mM 0.0257 mL 0.1287 mL 0.2574 mL 0.6436 mL
100 mM 0.0206 mL 0.1030 mL 0.2060 mL 0.5149 mL
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QL-1200186 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

QL-12001862848664-42-4QL1200186QL 1200186STATInterleukin RelatedIFNARILInterferon-α/β receptorInterferon-alpha/beta receptorAllosteric inhibitorAutoimmune diseasesCytokine pathwayJAKPseudokinase regulatory domainPsoriasisTYK2Inhibitorinhibitorinhibit

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