| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
AZD-8154 targets PI3Kgamma (IC50=9.2 microM) and PI3Kdelta (IC50=7.2 microM) isoforms. These lipid kinases are predominantly expressed in leukocytes and are key signaling hubs downstream of various immune receptors, including T-cell receptors, B-cell receptors, and cytokine receptors. By inhibiting both PI3Kgamma and PI3Kdelta, the compound suppresses the activation of immune cells involved in allergic and inflammatory responses.
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| ln Vitro |
At concentrations ranging from 0.1 to 1000 nM, AZD-8154 inhibits the expression of the activation markers CD11b and CD86 on B cells isolated from rat spleen, demonstrating its ability to suppress immune cell activation. The dual inhibition of PI3Kgamma and PI3Kdelta pathways leads to a broad suppression of mast cell, neutrophil, and T-cell functions relevant to the pathogenesis of asthma.
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| ln Vivo |
In an OVA (ovalbumin)-induced rat model of allergic asthma, AZD-8154 is administered via the intratracheal route at doses of 0.02, 0.1, and 0.3 mg/kg. The compound is given one hour prior to OVA challenge on day 28. At a dose of 0.3 mg/kg, AZD-8154 significantly reduces airway inflammation and the late asthmatic response (LAR), demonstrating its in vivo efficacy in a clinically relevant model of asthma.
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| Enzyme Assay |
Specific protocols for the binding assay are not detailed; however, PI3Kgamma/delta biochemical activity is typically measured using a fluorescence polarization (FP) or homogeneous time-resolved fluorescence (HTRF) assay. The purified PI3Kgamma/delta enzyme is incubated with phosphatidylinositol (4,5)-bisphosphate (PIP2) and ATP in the presence of varying concentrations of AZD-8154. After the reaction, the amount of PIP3 produced is detected via a specific binding protein (e.g., GRP1 PH domain) labeled with a fluorophore to calculate the IC50.
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| Cell Assay |
Rat splenocytes or primary B cells are isolated and cultured in vitro. Cells are pre-treated with varying concentrations of AZD-8154 (0.1-1000 nM) and then stimulated with an activating agent (e.g., anti-IgM for B cells). After incubation, the expression of activation markers like CD11b and CD86 on the cell surface is measured by flow cytometry to quantify the compound's inhibitory effect on immune cell activation.
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| Animal Protocol |
In an OVA-induced allergic asthma rat model, female Brown Norway rats are sensitized with ovalbumin (OVA) on days 0, 14, and 21. On day 28, the rats are challenged with an intratracheal instillation of OVA. AZD-8154 (or vehicle) is administered intratracheally one hour prior to the OVA challenge. Airway responsiveness to methacholine is measured 24 hours post-challenge using a whole-body plethysmograph. Bronchoalveolar lavage (BAL) is performed to count inflammatory cells (eosinophils, neutrophils) and measure Th2 cytokines.
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| ADME/Pharmacokinetics |
Specific PK parameters for AZD-8154 are not detailed. As an inhaled drug candidate, the key pharmacokinetic property is its high local lung exposure combined with low systemic bioavailability to maximize efficacy while minimizing systemic toxicities commonly associated with oral PI3Kdelta inhibitors, such as transaminitis and colitis. Its half-life in the lung and clearance rate are critical parameters for its inhaled formulation.
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| Toxicity/Toxicokinetics |
Specific toxicological data for AZD-8154 are not provided in the literature. However, known class-related toxicities of PI3Kdelta and PI3Kgamma inhibitors include potential immunosuppression and infections. The rationale for developing AZD-8154 as an inhaled agent is to mitigate these systemic toxicities by restricting the compound's action primarily to the lung, thereby aiming for an improved therapeutic index.
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| References | |
| Additional Infomation |
AZD-8154 is an investigational, research-grade compound that has been evaluated in pre-clinical disease models. Its distinct profile as an inhaled, dual PI3Kgamma/delta inhibitor targets a key immune mechanism in asthma while aiming to overcome the tolerability issues of earlier systemic PI3K inhibitors. As of the latest updates, this compound has been used for advanced pharmaceutical research and has not yet been approved for medical use.
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| Molecular Formula |
C27H29N5O4S2
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|---|---|
| Molecular Weight |
551.680263280869
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| Exact Mass |
551.166
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| CAS # |
2215022-45-8
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| PubChem CID |
141754136
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
1030
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S(C)(C1=CC(C2=C(C)N=C(NC3=CC=CC(=N3)N3C(CCC3)=O)S2)=CC2=C1C(N(C2)[C@@H](C)C1CC1)=O)(=O)=O
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| InChi Key |
XOMFDZJQLSPGGV-INIZCTEOSA-N
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| InChi Code |
InChI=1S/C27H29N5O4S2/c1-15-25(37-27(28-15)30-21-6-4-7-22(29-21)31-11-5-8-23(31)33)18-12-19-14-32(16(2)17-9-10-17)26(34)24(19)20(13-18)38(3,35)36/h4,6-7,12-13,16-17H,5,8-11,14H2,1-3H3,(H,28,29,30)/t16-/m0/s1
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| Chemical Name |
2-[(1S)-1-cyclopropylethyl]-5-[4-methyl-2-[[6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-3H-isoindol-1-one
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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 : ~25 mg/mL (~45.32 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 | 1.8126 mL | 9.0632 mL | 18.1265 mL | |
| 5 mM | 0.3625 mL | 1.8126 mL | 3.6253 mL | |
| 10 mM | 0.1813 mL | 0.9063 mL | 1.8126 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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