| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 2 nM (FLAP)[1].
5-Lipoxygenase activating protein (FLAP). Atuliflapon (AZD5718) is an orally active inhibitor of FLAP (5-lipoxygenase activating protein). FLAP is an essential protein that facilitates the transfer of arachidonic acid to 5-lipoxygenase (5-LO) for the biosynthesis of leukotrienes. By inhibiting FLAP, Atuliflapon attenuates the 5-lipoxygenase pathway and reduces the production of pro-inflammatory and vasoactive leukotrienes. The compound has an IC50 of 2.0 nM for FLAP inhibition. |
|---|---|
| ln Vitro |
Leukotriene synthesis is dose-dependently inhibited by atuliflapon [1]. For LTB4, atuliflapon exhibits an IC50 of 39 nM[1].
Atuliflapon inhibits FLAP with an IC50 of 2.0 nM, attenuating the 5-lipoxygenase pathway and reducing pro-inflammatory and vasoactive leukotriene production. The compound's potent FLAP inhibition makes it a valuable tool for studying the role of leukotrienes in inflammation and cardiovascular disease. In vitro studies have demonstrated an IC50 of 39 nM for the compound's effect on leukotriene production. |
| ln Vivo |
The half-life (t1/2) of AtuLiflapon administered intravenously is 0.45 hours in rats and 2.1 hours in dogs [1]. In mouse blood, AtuLiflapon does not exhibit suppression of 5-LO pathway activity [1].
In vivo, Atuliflapon has been investigated for the treatment of coronary artery disease. As an orally active compound, it can be administered conveniently for chronic treatment. By inhibiting FLAP and reducing leukotriene production, Atuliflapon may reduce inflammation and improve cardiovascular outcomes. Clinical studies have been conducted to evaluate the efficacy and safety of Atuliflapon in patients with coronary artery disease. |
| Enzyme Assay |
FLAP binding assays are used to measure the inhibitory activity of Atuliflapon. Radioligand binding assays or fluorescence polarization assays are performed using FLAP protein and a labeled FLAP ligand. Increasing concentrations of Atuliflapon are added to determine the IC50 for inhibition of FLAP binding. The reported IC50 is 2.0 nM.
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| Cell Assay |
Cellular assays using leukotriene-producing cells (e.g., human neutrophils or mast cells) are employed to evaluate the functional inhibition of Atuliflapon. Cells are stimulated with calcium ionophore or other agonists in the presence of increasing concentrations of Atuliflapon. Leukotriene B4 and C4 production is measured by ELISA to determine the compound's inhibitory effects on the 5-lipoxygenase pathway. The IC50 for leukotriene production is approximately 39 nM.
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| Animal Protocol |
In vivo efficacy of Atuliflapon has been evaluated in preclinical and clinical studies for coronary artery disease. The compound is administered orally. Efficacy endpoints include reduction of leukotriene levels, improvement in inflammatory markers, and cardiovascular outcomes. Clinical studies have been conducted to assess the compound's potential for treating coronary artery disease.
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| ADME/Pharmacokinetics |
As an orally active small molecule with molecular weight of 446.50 g/mol and molecular formula C24H26N6O3, Atuliflapon is administered orally. The compound is soluble in DMSO (89 mg/mL) and has moderate solubility in ethanol (3 mg/mL). It is insoluble in water. Pharmacokinetic properties support once-daily oral dosing. The compound has been investigated in clinical trials for coronary artery disease.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have evaluated the safety of Atuliflapon in animal models. As a FLAP inhibitor that reduces leukotriene production, potential toxicities include effects on immune function and host defense. Standard toxicology assessments include evaluation of organ toxicity, genotoxicity, and reproductive toxicity. Clinical trials have assessed the safety profile in patients with coronary artery disease.
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| References | |
| Additional Infomation |
Atuliflapon is currently undergoing the clinical trial NCT05251259 (a study evaluating the efficacy and safety of atuliflapon in the treatment of moderate to severe uncontrolled asthma).
5-Lipoxygenase-activated protein inhibitor Atuliflapon (also known as AZD5718) is an orally active, potent inhibitor of 5-lipoxygenase activating protein (FLAP). It attenuates the 5-lipoxygenase pathway and reduces pro-inflammatory leukotriene production. The compound has an IC50 of 2.0 nM for FLAP inhibition and an IC50 of 39 nM for leukotriene production. Atuliflapon has the potential to treat coronary artery disease. CAS: 2041075-86-7. |
| Molecular Formula |
C24H26N6O3
|
|---|---|
| Molecular Weight |
446.501644611359
|
| Exact Mass |
446.206
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| CAS # |
2041075-86-7
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| PubChem CID |
122678117
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
755
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| Defined Atom Stereocenter Count |
2
|
| SMILES |
O=C(C1C=CC(C2C=C(C)NN=2)=CC=1)[C@@H]1CCCC[C@H]1C(NC1C=NN2CCNC(C2=1)=O)=O
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| InChi Key |
ROTWSDMXHVGAHZ-QZTJIDSGSA-N
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| InChi Code |
InChI=1S/C24H26N6O3/c1-14-12-19(29-28-14)15-6-8-16(9-7-15)22(31)17-4-2-3-5-18(17)23(32)27-20-13-26-30-11-10-25-24(33)21(20)30/h6-9,12-13,17-18H,2-5,10-11H2,1H3,(H,25,33)(H,27,32)(H,28,29)/t17-,18-/m1/s1
|
| Chemical Name |
(1R,2R)-2-[4-(5-methyl-1H-pyrazol-3-yl)benzoyl]-N-(4-oxo-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-3-yl)cyclohexane-1-carboxamide
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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: 125 mg/mL (279.96 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.66 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 (4.66 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 (4.66 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 | 2.2396 mL | 11.1982 mL | 22.3964 mL | |
| 5 mM | 0.4479 mL | 2.2396 mL | 4.4793 mL | |
| 10 mM | 0.2240 mL | 1.1198 mL | 2.2396 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05251259
Conditions:AsthmaLink: https://clinicaltrials.gov/ct2/show/NCT04601467
Conditions:Acute Coronary SyndromeLink: https://clinicaltrials.gov/ct2/show/NCT04492722
Conditions:Chronic Kidney Disease
Title:Study to Assess Relative Bioavailability and Safety of AZD5718 in Healthy Volunteers
Status:Completed
updateDate:2021-12-06
Ctid:NCT04734275
Link: https://clinicaltrials.gov/ct2/show/NCT04734275
Conditions:Chronic Kidney DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT03317002
Conditions:Coronary Artery DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT04492709
Conditions:Cardiovascular DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT04210388
Conditions:Coronary Artery Disease (CAD)Link: https://clinicaltrials.gov/ct2/show/NCT02632526
Conditions:Healthy Male Subjects|Cardiovascular DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT03400488
Conditions:Coronary Artery DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT03420092
Conditions:Coronary Artery DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT02963116
Conditions:High Risk Coronary Artery DiseaseProducts are for research use only; We do not sell to patients
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