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| Targets |
AZD8848 targets Toll-like receptor 7 (TLR7), a pattern recognition receptor that plays a critical role in the innate immune response to viral RNA. It is a selective TLR7 prodrug agonist with pEC50 values of 7.0 for human TLR7 and 6.6 for TLR7-adsorbed cells. AZD8848 has no activity against human TLR8 or TLR1. Upon activation, TLR7 signaling induces the production of type I interferons and pro-inflammatory cytokines, which modulate immune responses.
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| ln Vitro |
AZD8848 demonstrates strong anti-TLR7 action, with pEC50 values for human TLR7 and TLR7-adsorbed cells being 7.0 and 6.6, respectively [1]. Regardless of whether PHA polyclonal or inhibitory presentation is used to boost T cells, AZD8848 has an EC50 of 4 nM when generating IFNα in human peripheral blood mononuclear cells and an IC50 of 0.2-1.0 nM when blocking IL-5 [1]. Locally inhibiting Th2 responses, AZD8848 is a strong and selective prodrug of TLR7 agonist [1]. AZD8848 has no anti-human TLR8 or anti-tLR1 action [1].
In vitro, AZD8848 demonstrates potent anti-TLR7 activity and inhibits Th2 responses. It has an EC50 of 4 nM for generating IFNα in human peripheral blood mononuclear cells and an IC50 of 0.2-1.0 nM for blocking IL-5 production. The compound shows no activity against human TLR8 or TLR1, confirming its selectivity for TLR7. AZD8848 locally inhibits Th2 responses, making it a valuable tool for studying innate immunity and respiratory conditions. |
| ln Vivo |
In Brown's Norway, AZD8848 (0.1–1 mg/kg; intratracheal) exhibits favorable pharmacokinetics [1]. Ovalbumin (OVA) response is inhibited by AZD8848 (0.3 mg/kg; intratracheal) Response model
In vivo, AZD8848 exhibits favorable pharmacokinetics in Brown Norway rats following intratracheal administration at 0.1-1 mg/kg. It inhibits ovalbumin (OVA) responses in a dose-dependent manner at 0.3 mg/kg intratracheally. The compound has a very short half-life in rat blood (0.2 minutes), with levels remaining above 1000 nmol/kg for more than 5 hours. AZD8848 has been studied in clinical trial NCT01818869 evaluating its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for AZD8848 measure its binding affinity and agonistic activity at TLR7. Receptor binding assays are performed using membranes from cells expressing human TLR7 and a radiolabeled ligand. Functional assays measure the activation of TLR7-mediated signaling, such as NF-κB activation or interferon production. The pEC50 values for human TLR7 and TLR7-adsorbed cells are 7.0 and 6.6, respectively. Selectivity is confirmed by testing against TLR8 and TLR1, where no activity is observed.
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| Cell Assay |
In vitro cell-based assays for AZD8848 are conducted using human peripheral blood mononuclear cells (PBMCs) or TLR7-expressing cell lines. Cells are treated with AZD8848 at various concentrations, and the production of IFNα and other cytokines is measured by ELISA. The EC50 for IFNα production is 4 nM. For Th2 response studies, cells are stimulated to produce IL-5, and the inhibition of IL-5 production is measured, with an IC50 of 0.2-1.0 nM. These assays confirm the compound's potent and selective TLR7 agonist activity.
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| Animal Protocol |
Animal/Disease Models: Brown Norway rat allergy model [1]
Doses: 0.1 mg/kg, 1 mg/kg Route of Administration: intratracheal ( 24 hrs (hrs (hours)) before OVA challenge and 24 hrs (hrs (hours)) after OVA challenge) Experimental Results: Inhibited OVA challenge in a dose-dependent manner. Animal/Disease Models: Norwegian brown rat[1] Doses: 0.3 mg/kg (pharmacokinetic/PK/PK analysis) Mode of Route of Administration: Intratracheal Experimental Results: Very short half-life in rat blood (0.2 minutes), with a slow decline thereafter, levels Above 1000 nmol/kg for more than 5 hrs (hrs (hours)). In vivo animal experiments for AZD8848 are conducted in Brown Norway rat models of allergic airway inflammation. In a typical study, rats are sensitized with ovalbumin (OVA) and then challenged with OVA. AZD8848 is administered intratracheally at doses of 0.1-1 mg/kg. The compound's ability to inhibit OVA-induced airway inflammation is assessed by measuring inflammatory cell infiltration, cytokine levels, and airway hyperresponsiveness. AZD8848 has been shown to inhibit OVA responses in a dose-dependent manner. |
| ADME/Pharmacokinetics |
AZD8848 has a molecular weight of 569.7 g/mol and a molecular formula of C29H43N7O5. It has a logP of 2.3. The compound is a white to off-white solid powder. It is soluble in DMSO and other organic solvents. For storage, it is recommended to keep the powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. The compound is stable at ambient temperature for a few days during shipping. Pharmacokinetic studies in rats show a very short half-life in blood (0.2 minutes), with levels remaining above 1000 nmol/kg for more than 5 hours.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for AZD8848 is not provided in standard product descriptions. As a compound that has been investigated in clinical trials (NCT01818869), its safety profile has been evaluated in human studies. The compound is designed as an antedrug agonist to minimize systemic exposure and potential toxicity. As with all research chemicals, standard laboratory safety precautions should be followed when handling AZD8848. Its use is limited to research applications and it is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
AZD-8848 is being studied in the clinical trial NCT01818869 (evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of AZD8848 in healthy subjects).
AZD8848 is a research compound and is not approved for any clinical or therapeutic use. It is a selective TLR7 prodrug agonist developed for the research of asthma and allergic rhinitis. The compound is an imidazoquinoline derivative that acts as an antedrug agonist, designed to be activated locally to modulate innate immune responses while minimizing systemic exposure. AZD8848 has been studied in clinical trial NCT01818869 evaluating its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects. Its mechanism of action involves activating TLR7 signaling to induce type I interferons and modulate Th2 responses. |
| Molecular Formula |
C29H43N7O5
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| Molecular Weight |
569.695626497269
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| Exact Mass |
569.332
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| CAS # |
866269-28-5
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| PubChem CID |
11592228
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
41
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| Complexity |
802
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FEFIBEHSXLKJGI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H43N7O5/c1-3-4-16-41-28-32-26(30)25-27(33-28)36(29(38)31-25)13-7-12-35(11-6-10-34-14-17-40-18-15-34)21-23-9-5-8-22(19-23)20-24(37)39-2/h5,8-9,19H,3-4,6-7,10-18,20-21H2,1-2H3,(H,31,38)(H2,30,32,33)
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| Chemical Name |
methyl 2-[3-[[3-(6-amino-2-butoxy-8-oxo-7H-purin-9-yl)propyl-(3-morpholin-4-ylpropyl)amino]methyl]phenyl]acetate
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| Synonyms |
AZD8848 AZD 8848 AZD-8848
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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 (~43.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.39 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 25.0 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: 2.5 mg/mL (4.39 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.39 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 | 1.7553 mL | 8.7765 mL | 17.5531 mL | |
| 5 mM | 0.3511 mL | 1.7553 mL | 3.5106 mL | |
| 10 mM | 0.1755 mL | 0.8777 mL | 1.7553 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01818869 | COMPLETED | Drug: AZD8848 Drug: Placebo to match AZD8848 |
Healthy Subjects Safety, Tolerability, |
AstraZeneca | 2014-01 | Phase 1 |
| NCT01205867 | COMPLETED | Drug: AZD8848 | Butyrylcholinesterase Deficiency | AstraZeneca | 2010-09 | Phase 1 |
| NCT01203124 | COMPLETED | Drug: AZD8848 Drug: Placebo |
Healthy Volunteers | AstraZeneca | 2010-11 | Phase 1 |
| NCT00770003 | COMPLETED | Drug: AZD8848 Drug: Placebo |
Allergic Rhinitis | AstraZeneca | 2008-09 | Phase 1 |
| NCT00688779 | COMPLETED | Drug: AZD8848 Drug: Placebo |
Allergic Rhinitis Healthy |
AstraZeneca | 2008-01 | Phase 1 |
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