| Size | Price | Stock | Qty |
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| Targets |
AS2863619 targets cyclin-dependent kinase 8 (CDK8) and CDK19. It inhibits these kinases, which are components of the Mediator complex and regulate transcription. By inhibiting CDK8/19, AS2863619 enhances the activation of STAT5, which in turn activates the Foxp3 gene, promoting the differentiation of T cells into regulatory T (Treg) cells.
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| ln Vitro |
When mouse CD4+ T cells were treated with AS2863619 (1 μM) for 22 hours, the amount of serine phosphorylation of the STAT5b PSP motif was reduced to around 40%, whereas the amount of tyrosine phosphorylation of the C-terminal domain was increased to about 160% of the samples treated with control. %[1].
In vitro, AS2863619 (1 µM) inhibits the serine phosphorylation of the STAT5b PSP motif to approximately 40% while enhancing tyrosine phosphorylation of the C-terminal domain to about 160% of control levels in mouse CD4+ T cells. This modulation of STAT5 phosphorylation promotes Foxp3 expression and Treg cell differentiation. The compound shows potent inhibition of CDK8 and CDK19 with low nanomolar IC50 values. |
| ln Vivo |
AS2863619 (30 mg/kg; oral; daily; for 2 weeks; mice) Treatment after sensitization with 2,4-dinitrofluorobenzene (DNFB) inhibits the extent of secondary reactions and infiltration of inflammatory cells into the skin Less severe and reduced ratio of changes in interferon-gamma+ (IFN-γ+) cells in a skin contact hypersensitivity model compared to vehicle-treated control mice. Eliminating Tregs before evoking secondary responses eliminated AS2863619-induced suppression. KLRG1+ Foxp3+ T cells were specifically enhanced in DNFB-sensitized AS2863619-treated animals [1].
In vivo, AS2863619 (30 mg/kg; oral; daily for 2 weeks) inhibits secondary reactions and reduces infiltration of inflammatory cells in a DNFB-induced skin contact hypersensitivity model in mice. It specifically enhances KLRG1+ Foxp3+ T cells in sensitized animals. The immunosuppressive effect is dependent on Tregs, as eliminating Tregs abolished AS2863619-induced suppression. |
| Enzyme Assay |
The in vitro enzyme assay for AS2863619 involves measuring the inhibition of CDK8 and CDK19 kinase activity. Recombinant kinases are incubated with substrates and ATP in the presence of varying compound concentrations. The IC50 values are determined by quantifying the reduction in substrate phosphorylation using techniques such as radioactive or fluorescence-based assays.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Mouse CD4+ T cells Tested Concentrations: 1 μM Incubation Duration: 22 hrs (hours) Experimental Results: Inhibited the serine phosphorylation of the PSP motif of STAT5b to approximately 40%, while inhibiting the tyrosine phosphorylation of the PSP motif of STAT5b to about 40%, while inhibiting the tyrosine phosphorylation of the PSP motif of STAT5b. Amino acid phosphorylation was enhanced to approximately 160% of the control treated sample. Cellular assays are performed using mouse CD4+ T cells treated with AS2863619 (1 µM) for 22 hours. Western blot analysis is used to assess the phosphorylation status of STAT5 and the expression of Foxp3. The conversion of effector/memory T cells into Foxp3+ regulatory T cells is measured by flow cytometry. |
| Animal Protocol |
Animal/Disease Models: DNFB-induced contact skin allergy in mice [1]
Doses: 30 mg/kg Route of Administration: oral; daily; lasting for 2 weeks Experimental Results: secondary reaction degree, inflammatory cells infiltration into the skin was light, interferon diminished proportion of -γ+ (IFN-γ+) cells. In vivo animal studies are conducted in a DNFB-induced contact skin allergy model in mice. AS2863619 is administered orally at 30 mg/kg daily for 2 weeks. The severity of skin reactions, inflammatory cell infiltration, and the proportion of IFN-γ+ cells are assessed to evaluate the compound's immunosuppressive effects. Treg depletion experiments are performed to confirm the mechanism of action. |
| ADME/Pharmacokinetics |
AS2863619 is an orally active compound with good bioavailability. It can be administered orally in vivo, indicating favorable pharmacokinetic properties. The compound is soluble in DMSO and can be formulated for both in vitro and in vivo use. Specific PK parameters such as half-life, Cmax, and AUC are not detailed in the available sources.
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| Toxicity/Toxicokinetics |
Toxicity data for AS2863619 are not reported in the available sources. As an investigational compound, it is used for research purposes only. The compound has been evaluated in animal models at doses up to 30 mg/kg without obvious toxicity reported in the described studies. Specific toxicological profiles are not available.
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| References | |
| Additional Infomation |
AS2863619 is a research tool for studying CDK8/19-mediated transcriptional regulation and immune modulation. It is particularly useful for investigating Treg cell differentiation and the development of immunotherapies for autoimmune diseases and cancer. The compound is available from chemical suppliers for research use only.
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| Molecular Formula |
C16H12N8O
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| Molecular Weight |
332.319480895996
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| Exact Mass |
332.113
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| CAS # |
2241300-50-3
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| Related CAS # |
AS2863619;2241300-51-4
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| PubChem CID |
139600292
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| Appearance |
White to off-white solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
495
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1N=C(C(C2=NC3C=NC=CC=3N2C2=CC=C3C(=C2)NC(C)=N3)=N1)N
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| InChi Key |
OORKHRHPVSWORX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H12N8O/c1-8-19-10-3-2-9(6-11(10)20-8)24-13-4-5-18-7-12(13)21-16(24)14-15(17)23-25-22-14/h2-7H,1H3,(H2,17,23)(H,19,20)
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| Chemical Name |
4-[1-(2-methyl-3H-benzimidazol-5-yl)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine
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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 : ~250 mg/mL (~752.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0091 mL | 15.0457 mL | 30.0915 mL | |
| 5 mM | 0.6018 mL | 3.0091 mL | 6.0183 mL | |
| 10 mM | 0.3009 mL | 1.5046 mL | 3.0091 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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