| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C26H27N7O3 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
QL-1200186 is a selective, orally active, allosteric inhibitor of the TYK2 pseudokinase domain JH2 (IC50 0.06 nM), with 164-fold selectivity over TYK1 JH2 (IC50 9.85 nM). It stabilizes the TYK2 JH2 conformation, inhibits the JH1 catalytic domain, and blocks IFNα- and IL-12/IL-23-mediated JAK-STAT signaling, and can reduce production of Th1/Th17-related cytokines such as IFNγ and IL-23 and lower immune cell activation, with no significant effect on JAK1/2/3 activity. In an imiquimod-induced psoriasis mouse model it can significantly improve skin inflammation and lower the Psoriasis Area and Severity Index (PASI) score, and it can be used to study autoimmune diseases such as psoriasis and systemic lupus erythematosus (SLE)[1]. It is supplied as a white to off-white solid (C26H27N7O3, MW 485.54) at 99.95% purity.
Physical & Chemical Properties
| CAS Number | 2848664-42-4 |
|---|---|
| Molecular Formula | C26H27N7O3 |
| Molecular Weight | 485.54 g/mol |
| Purity | 99.95% |
| 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 |
| Target | IL-12, IL-23, STAT1, STAT3, STAT5 |
| Signaling Pathway | JAK/STAT Signaling; Stem Cell/Wnt; Immunology/Inflammation |
| Solubility | In Vitro: DMSO: 100 mg/mL (205.96 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 6 months; -20°C, 1 month. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 100 mg/mL (205.96 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 2.5 mg/mL (5.15 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 2
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 2.5 mg/mL (5.15 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 900 μL corn oil. |
Data provided by the manufacturer.
In Vitro
QL-1200186 (1-10 μM; 30 min+15 min) suppresses 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 are 32.48 nM for IL-12-induced IFN-γ expression and 1.026 nM for IL-23-induced pSTAT3, respectively[1]. In human PBMCs, QL-1200186 (1-10 μM; 48 h) blocks IFNα-induced pSTAT5 with an IC50 of 7.26 nM[1].
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. |
In Vivo
In an IL-12/IL-18-induced mouse inflammation model, QL-1200186 (1-10 mg/kg; oral; once daily; 3 days) lowers serum IFNγ levels in a dose-dependent manner, and the highest inhibition rate reaches 97.8%[1]. In an Imiquimod-induced mouse psoriasis model, QL-1200186 (5-30 mg/kg; oral; twice daily; 7 days) significantly decreases PASI scores and improves skin erythema, scaling and thickening; skin thickness falls by 49.7% in the 30 mg/kg group[1].
| 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. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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