| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
PI3Kγ (IC50 = 70 nM); PI3Kα (IC50 = 240 nM); PI3Kβ (IC50 = 1.4 μM); PI3Kδ (IC50 = 1.7 μM)
AS-041164 targets Phosphoinositide 3-kinase gamma (PI3Kγ) (Ki = 0.1 μM) [1] |
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| ln Vitro |
AS-041164 potently inhibited the activity of recombinant PI3Kγ with a Ki value of 0.1 μM, while showing weak inhibitory effects on PI3Kα, PI3Kβ, and PI3Kδ subtypes (selectivity >100-fold vs PI3Kγ) [1]
AS-041164 dose-dependently inhibited neutrophil chemotaxis induced by fMLP or CXCL8, with significant inhibition (≥50%) observed at concentrations of 1-10 μM [1] AS-041164 reduced the adhesion of neutrophils to endothelial cells in vitro without affecting neutrophil phagocytic function [1] AS-041164 decreased reactive oxygen species (ROS) production in neutrophils stimulated by PMA, as detected by flow cytometry with a fluorescent probe [1] |
| ln Vivo |
In the model of carrageenan-induced paw edema, treatment with AS-041164 (10–100 mg/kg; oral administration; once) reduces inflammatory swelling[1]. AS-041164 (3-100 mg/kg p.o.) treatment dose-dependently decreases r-h regulated on activation normal T cell expressed and secreted (RANTES)-induced neutrophil recruitment in mice. As for AS-041164, the ED50 value is 27.35 mg/kg. AKT phosphorylation is decreased and chemotaxis caused by RANTES is blocked by AS-041164[1].
In mice with carrageenan-induced paw edema, oral administration of AS-041164 (1, 10, 30 mg/kg) dose-dependently inhibited paw swelling, with an inhibition rate of ~60% at 30 mg/kg (measured 6 hours after carrageenan injection) [1] In carrageenan-induced pleurisy in mice, oral AS-041164 (30 mg/kg) significantly reduced the number of neutrophils in pleural exudate by ~70% compared with the control group [1] In LPS-induced peritonitis in mice, intraperitoneal injection of AS-041164 (10 mg/kg) inhibited neutrophil infiltration into the peritoneal cavity [1] AS-041164 downregulated the levels of pro-inflammatory cytokines (CXCL1, TNF-α) in inflamed tissues of animal models [1] |
| Enzyme Assay |
Recombinant PI3Kγ protein was prepared and mixed with phospholipid substrate (PIP2), [γ-32P]ATP, and various concentrations of AS-041164 in a reaction buffer. The reaction was incubated at 30°C for a specified period and terminated by adding a stop solution. Phosphorylated products were separated by thin-layer chromatography (TLC), and radioactivity was quantified by autoradiography. The inhibition rate of PI3Kγ enzymatic activity was calculated, and the Ki value was derived by fitting the inhibition rate curve [1]
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| Cell Assay |
Neutrophils were isolated from mouse bone marrow or human peripheral blood and purified. For chemotaxis assays, neutrophils were added to the upper chamber of Transwell inserts, and chemokines (fMLP or CXCL8) plus different concentrations of AS-041164 were added to the lower chamber. After incubation at 37°C, the number of neutrophils migrated to the lower chamber was counted. For adhesion assays, endothelial cells were cultured to confluence in plates, then neutrophils and AS-041164 were added; non-adherent cells were washed away, and adherent neutrophils were counted. For ROS production assays, neutrophils were loaded with a fluorescent probe, treated with AS-041164, and stimulated; ROS levels were detected by flow cytometry [1]
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| Animal Protocol |
Male Wistar rats (100-150 g) injected with carrageenan[1]
10 mg/kg, 30 mg/kg, 100 mg/kg Oral administration; once Carrageenan-induced paw edema model: Male ICR mice (20-25 g) were orally administered AS-041164 (1, 10, 30 mg/kg) suspended in 0.5% carboxymethylcellulose sodium (CMC-Na) 1 hour before carrageenan injection. The control group received an equal volume of 0.5% CMC-Na. 1% carrageenan was subcutaneously injected into the right hind paw, and paw volume was measured at 1, 3, and 6 hours after injection to calculate swelling rate [1] Carrageenan-induced pleurisy model: Mice were intraperitoneally injected with 1% carrageenan to induce pleurisy. AS-041164 (30 mg/kg) was orally administered 1 hour before carrageenan injection. Mice were euthanized 24 hours later, pleural exudate was collected, and the number of neutrophils was counted [1] LPS-induced peritonitis model: Mice were intraperitoneally injected with LPS (1 mg/kg) to induce peritonitis. AS-041164 (10 mg/kg) was intraperitoneally administered 30 minutes before LPS injection. Six hours later, peritoneal lavage fluid was collected, and neutrophil infiltration was quantified [1] |
| Toxicity/Toxicokinetics |
At experimental doses (1-30 mg/kg), mice did not show obvious signs of toxicity, including no significant weight loss, behavioral abnormalities, or organ damage [1]
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| References | |
| Additional Infomation |
AS-041164 is a selective PI3Kγ inhibitor with very low cross-reactivity with other PI3K subtypes (α, β, δ) [1]. AS-041164 exerts its anti-inflammatory effect by blocking the PI3Kγ-mediated signaling pathway, thereby inhibiting the recruitment and activation of neutrophils in early inflammation [1]. AS-041164 does not impair the phagocytic function of neutrophils, indicating that it has good anti-inflammatory safety [1].
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| Molecular Formula |
C11H7NO4S
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|---|---|
| Molecular Weight |
249.24258
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| Exact Mass |
249.009
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| CAS # |
1146702-72-8
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| PubChem CID |
1269519
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Index of Refraction |
1.731
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| LogP |
1.56
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
17
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| Complexity |
395
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1OC2=C(O1)C=C(C=C2)/C=C\3/C(=O)NC(=O)S3
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| InChi Key |
SDGWAUUPHUBJNQ-WTKPLQERSA-N
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| InChi Code |
InChI=1S/C11H7NO4S/c13-10-9(17-11(14)12-10)4-6-1-2-7-8(3-6)16-5-15-7/h1-4H,5H2,(H,12,13,14)/b9-4-
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| Chemical Name |
(5Z)-5-(1,3-benzodioxol-5-ylmethylidene)-1,3-thiazolidine-2,4-dione
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| Synonyms |
AS-041164; AS041164; AS 041164; PI3Kγ inhibitor
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: ~125 mg/mL (501.5 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0122 mL | 20.0610 mL | 40.1220 mL | |
| 5 mM | 0.8024 mL | 4.0122 mL | 8.0244 mL | |
| 10 mM | 0.4012 mL | 2.0061 mL | 4.0122 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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