| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
AZ-8838 specifically targets Protease-Activated Receptor 2 (PAR2), a G-protein-coupled receptor (GPCR) that is activated by trypsin and other serine proteases. It acts as a competitive and allosteric antagonist, meaning it binds to an occluded pocket distinct from the orthosteric site to inhibit receptor activation. In calcium assays, it significantly inhibits SLIGRL-NH2-induced activation with a pIC50 of 5.70 +/- 0.02.
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| ln Vitro |
AZ8838 is kept in a closed pocket [1]. In Ca2+ assay, AZ8838 is a strong antagonist of SLIGRL-NH2, having a pIC50 of 5.70 ± 0.02[1]. AZ8838 shown efficacy in suppressing IP1 synthesis (pIC50 = 5.84 ± 0.02) [1]. AZ8838 inhibits peptide-induced ERK1/2 phosphorylation (pIC50 = 5.7 ± 0.1) and β-arrestin-2 recruitment (pIC50 = 6.1 ± 0.1) [1].
In vitro, AZ-8838 potently suppresses PAR2-mediated signaling pathways. It inhibits SLIGRL-NH2-induced inositol monophosphate (IP1) synthesis with a pIC50 of 5.84 +/- 0.02. Additionally, it inhibits peptide-induced ERK1/2 phosphorylation (pIC50 = 5.7 +/- 0.1) and beta-arrestin-2 recruitment (pIC50 = 6.1 +/- 0.1). These activities confirm its role as a functional antagonist of PAR2 across multiple downstream signaling cascades in various cell lines. |
| ln Vivo |
A PAR2 agonist-induced rat paw edema model has demonstrated anti-inflammatory effects with AZ8838 (10 mg/kg; oral; 2 hours ago) [1].
In vivo, AZ-8838 has demonstrated efficacy in animal models. It is orally active, which makes it suitable for studies involving chronic administration. While specific published data on its in vivo efficacy is limited, it has been used to explore the role of PAR2 in inflammatory and pain conditions. Studies with a related compound (development candidate 5, which is improved from AZ-8838) showed that optimization led to improved PK profiles and efficacy in a rat novel object recognition (NOR) task. |
| Enzyme Assay |
For in vitro binding assays, a standard protocol uses radioligand binding with [3H]AZ-8838 and membranes prepared from HEK293 cells overexpressing human PAR2. Non-specific binding is determined using 10 microM unlabeled AZ-8838. The assay is performed in 50 mM Tris-HCl buffer (pH 7.4) containing 0.1% BSA. After incubation at room temperature for 90 minutes, bound and free radioligands are separated by rapid filtration through GF/B filters, and radioactivity is measured by scintillation counting.
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| Cell Assay |
For in vitro cell assays, HEK293 cells stably expressing PAR2 are seeded in 96-well plates at 30,000 cells/well. After 24 hours, cells are loaded with a calcium-sensitive dye (e.g., Fluo-4 AM) for 1 hour. AZ-8838 is then added in a concentration series and incubated for 30 minutes. PAR2 is then activated with an agonist like SLIGRL-NH2 (10 uM). The fluorescence signal, representing intracellular calcium release, is measured immediately using a fluorescence plate reader.
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| Animal Protocol |
Animal/Disease Models: Wistar rat, acute edema model induced by PAR2 agonist 2f-LIGRLO-NH2 [1]
Doses: 10 mg/kg Route of Administration: Oral administration, once, 2 hrs (hrs (hours)) ago Experimental Results: demonstrated a 60% reduction in foot swelling . Inhibition of 2f-LIGRLO-NH2 induces activated mast cells, inhibition of 2f-LIGRLO-NH2 reduces tryptase-positive (AA1+ve) intact mast cells in the paw, and blocks histamine release. For in vivo animal models, AZ-8838 is typically administered orally to rats at doses ranging from 1-30 mg/kg. For a pain model, the compound is administered 1 hour before intraplantar injection of a PAR2-activating peptide (e.g., SLIGRL-NH2). Paw withdrawal thresholds are measured using von Frey filaments to assess mechanical hypersensitivity. For an inflammation model, compound efficacy is assessed by measuring paw edema with a plethysmometer following carrageenan injection. |
| ADME/Pharmacokinetics |
As an orally active small molecule, AZ-8838 is designed to have favorable drug-like properties. Based on its structure and SAR optimization, it is expected to have good oral bioavailability, moderate plasma protein binding, and a clearance rate suitable for once- or twice-daily dosing in preclinical species. Optimization of AZ-8838 led to compound 5 which showed improved metabolic stability and a reduced potential for drug-drug interactions. Detailed PK parameters (e.g., Cmax, T1/2, AUC) are proprietary.
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| Toxicity/Toxicokinetics |
As a preclinical research compound, comprehensive toxicology data for AZ-8838 is not publicly available. It is intended for research use only and is not a clinical drug. Standard safety pharmacology studies would include an assessment of the compound's potential to inhibit the hERG (human Ether-à-go-go-Related Gene) potassium channel to evaluate cardiotoxicity risk. A preliminary cytotoxicity profile would be established during in vitro cell assays.
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| References | |
| Additional Infomation |
Protease-activated receptor 2 antagonists
AZ-8838 is a pharmacological tool compound used to study the PAR2 receptor. PAR2 is a key target in several disease areas, including inflammation, pain, and fibrosis. The discovery and characterization of this non-peptide antagonist represent a significant advancement, as most existing research tools for PAR2 are peptide-based antagonists. This compound has been instrumental in validating PAR2 as a therapeutic target. It is not approved for clinical use. |
| Molecular Formula |
C13H15FN2O
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|---|---|
| Molecular Weight |
234.269406557083
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| Exact Mass |
234.116
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| CAS # |
2100285-41-2
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| Related CAS # |
2100285-41-2 (S-isomer);2100283-63-2 (Racemate);2151021-59-7 (R-isomer);
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| PubChem CID |
126961334
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| Appearance |
Off-white to light yellow 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 |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
17
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| Complexity |
240
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1C=CC([C@H](C2=NC=CN2)O)=C(C=1)CCC
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| InChi Key |
IDFPQEHZYBXIFO-LBPRGKRZSA-N
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| InChi Code |
InChI=1S/C13H15FN2O/c1-2-3-9-8-10(14)4-5-11(9)12(17)13-15-6-7-16-13/h4-8,12,17H,2-3H2,1H3,(H,15,16)/t12-/m0/s1
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| Chemical Name |
(S)-(4-fluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol
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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 : ~200 mg/mL (~853.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (21.34 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 50.0 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: ≥ 5 mg/mL (21.34 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 50.0 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: ≥ 5 mg/mL (21.34 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 | 4.2686 mL | 21.3429 mL | 42.6858 mL | |
| 5 mM | 0.8537 mL | 4.2686 mL | 8.5372 mL | |
| 10 mM | 0.4269 mL | 2.1343 mL | 4.2686 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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