Atuliflapon (AZD5718) is an orally bioactive FLAP (5-lipoxygenase-activating protein) inhibitor (antagonist) with IC50 of 2 nM. Atuliflapon may be utilized in the research of coronary artery disease.

Physicochemical Properties

Molecular Formula	C24H26N6O3
Molecular Weight	446.501644611359
Exact Mass	446.206
CAS #	2041075-86-7
PubChem CID	122678117
Appearance	White to off-white solid powder
LogP	2.5
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	755
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
InChi Key	ROTWSDMXHVGAHZ-QZTJIDSGSA-N
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
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	IC50: 2 nM (FLAP)[1].
ln Vitro	Leukotriene synthesis is dose-dependently inhibited by atuliflapon [1]. For LTB4, atuliflapon exhibits an IC50 of 39 nM[1].
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].
References	[1]. Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease. J Med Chem. 2019 May 9;62(9):4312-4324.

Solubility Data

Solubility (In Vitro)

DMSO: 125 mg/mL (279.96 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.