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| Targets |
STAT6 1.9 nM (IC50) CYP3A4
AS1810722 targets STAT6, a transcription factor that mediates IL-4 and IL-13 signaling and plays a central role in Th2 immune responses and allergic inflammation. It inhibits STAT6 with an IC50 of 1.9 nM, demonstrating potent activity. The compound also shows good CYP3A4 inhibition, which may influence its metabolism and drug-drug interaction profile. By blocking STAT6 activation, AS1810722 suppresses Th2 differentiation and the production of Th2-associated cytokines. |
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| ln Vitro |
AS1810722 (compound 24) has no effect on the production of IFN-γ but suppresses the synthesis of IL-4 with an IC50 of 2.4 nM [1].
AS1810722 demonstrates potent STAT6 inhibition with an IC50 of 1.9 nM. It shows a good CYP3A4 inhibition profile. Importantly, AS1810722 inhibits Th2 differentiation in vitro without affecting Th1 differentiation or eosinophil infiltration, indicating selectivity for the Th2 pathway. This selectivity is advantageous for studying allergic diseases where Th2 responses are pathogenic, while preserving protective Th1 responses. The compound's activity has been characterized in both biochemical and cellular assays. |
| ln Vivo |
In an antigen-induced mouse asthma paradigm called Infiltration, AS1810722 (Compound 24; 0.03-0.3 mg/kg; oral; 30 minutes before OVA exposure, 24 hours, and 48 hours after OVA exposure) suppresses pulmonary eosinophils in a dose-dependent manner[1]. In an antigen-induced mouse asthma model, AS1810722 suppresses Th2 differentiation in vitro with an IC50 of 2.4 nM following oral administration; it has no effect on the differentiation of type 1 helper T (Th1) cells or eosinophil infiltration[1].
AS1810722 demonstrates in vivo efficacy in antigen-induced mouse asthma models following oral administration. The compound's oral activity makes it suitable for convenient dosing in animal studies. In these models, AS1810722 suppresses Th2-mediated airway inflammation and hyperresponsiveness. Its ability to inhibit Th2 differentiation without affecting Th1 responses is particularly valuable for studying allergic diseases. Further research is needed to explore its full therapeutic potential in various allergic and atopic disease models. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for AS1810722 typically involves a STAT6 phosphorylation assay using recombinant STAT6 protein or cell lysates. The compound is incubated with STAT6 in the presence of ATP, and the level of phosphorylated STAT6 is measured using an ELISA or Western blot with phospho-specific antibodies. Alternatively, a STAT6-DNA binding assay can be performed using an electrophoretic mobility shift assay (EMSA) or a colorimetric ELISA-based DNA-binding assay to assess the compound's ability to block STAT6 transcriptional activity. CYP3A4 inhibition is assessed using standard cytochrome P450 inhibition assays.
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| Cell Assay |
The in vitro cellular assay for AS1810722 typically uses Th2 differentiation assays with primary T cells or relevant cell lines. Cells are treated with varying concentrations of the compound under Th2-polarizing conditions (IL-4 stimulation), and the differentiation into Th2 cells is assessed by measuring Th2 cytokine production (e.g., IL-4, IL-5, IL-13) using ELISA or intracellular cytokine staining. STAT6 phosphorylation is measured by Western blot. The compound's selectivity for Th2 over Th1 differentiation is confirmed by comparing its effects under Th1-polarizing conditions.
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| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse asthmatic model by intraperitoneal (ip) injection of ovalbumin (OVA)-containing aluminum hydroxide gel[1]
Doses: 0.03-0.3 mg/kg Route of Administration: po (oral gavage) 30 min before, and 24 and 48 h after OVA exposure Experimental Results: Suppressed eosinophil infiltration in the lung in a dose-dependent manner. In vivo animal studies for AS1810722 typically involve antigen-induced mouse asthma models. Mice are sensitized and challenged with an antigen such as ovalbumin to induce allergic airway inflammation. AS1810722 is administered orally at various doses, and endpoints include airway hyperresponsiveness measured by methacholine challenge, eosinophil infiltration in bronchoalveolar lavage fluid, Th2 cytokine levels in lung tissue, and histological assessment of airway inflammation. The compound's effect on Th1/Th2 balance is also evaluated. |
| ADME/Pharmacokinetics |
AS1810722 is an orally active compound with favorable pharmacokinetic properties. It is a fused bicyclic pyrimidine derivative with a molecular weight of 477.51 and a formula of C25H25F2N7O. The compound is soluble in DMSO at 62.5 mg/mL (130.89 mM). Specific ADME parameters such as half-life, bioavailability, and clearance are not detailed in the available literature. The compound's oral activity and efficacy in asthma models suggest reasonable bioavailability and systemic exposure.
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| Toxicity/Toxicokinetics |
Toxicity data for AS1810722 are not extensively reported. As a research compound, comprehensive toxicological evaluations have not been performed. The compound is intended for laboratory research use only and should be handled with standard safety precautions. Appropriate personal protective equipment should be worn when handling this compound. Consult the Material Safety Data Sheet for specific safety and handling information.
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| References | |
| Additional Infomation |
AS1810722 is an orally active, potent STAT6 inhibitor (IC50 = 1.9 nM) with potential for studying allergic diseases such as asthma and atopic conditions. It inhibits Th2 differentiation without affecting Th1 responses, demonstrating pathway selectivity. The compound shows efficacy in antigen-induced mouse asthma models following oral administration. AS1810722 also exhibits CYP3A4 inhibition, which may have implications for its metabolism. It is not in clinical trials and has not been approved for therapeutic use. It remains a research tool for studying STAT6 biology and allergic inflammation.
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| Molecular Formula |
C25H25F2N7O
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| Molecular Weight |
477.509111166
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| Exact Mass |
477.208
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| CAS # |
909561-15-5
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| PubChem CID |
44208030
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| Appearance |
Brown to black solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
691
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=C(C=C(C=1)CN1C=CC2=CN=C(N=C12)NC1C=CC(=CC=1)N1CCN(CC(N)=O)CC1)F
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| InChi Key |
IJFRMEXSGYTWGY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H25F2N7O/c26-19-11-17(12-20(27)13-19)15-34-6-5-18-14-29-25(31-24(18)34)30-21-1-3-22(4-2-21)33-9-7-32(8-10-33)16-23(28)35/h1-6,11-14H,7-10,15-16H2,(H2,28,35)(H,29,30,31)
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| Chemical Name |
2-[4-[4-[[7-[(3,5-difluorophenyl)methyl]pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]acetamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 62.5 mg/mL (130.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.36 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0942 mL | 10.4710 mL | 20.9420 mL | |
| 5 mM | 0.4188 mL | 2.0942 mL | 4.1884 mL | |
| 10 mM | 0.2094 mL | 1.0471 mL | 2.0942 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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