AZD8848 is a selective TLR7 prodrug agonist studied in asthma and allergic rhinitis.

Physicochemical Properties

Molecular Formula	C29H43N7O5
Molecular Weight	569.695626497269
Exact Mass	569.332
CAS #	866269-28-5
PubChem CID	11592228
Appearance	White to off-white solid powder
LogP	2.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	17
Heavy Atom Count	41
Complexity	802
Defined Atom Stereocenter Count	0
InChi Key	FEFIBEHSXLKJGI-UHFFFAOYSA-N
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)
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
Synonyms	AZD8848 AZD 8848 AZD-8848
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

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].
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
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)).
References	[1]. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848. BMJ Open Respir Res. 2016 Feb 23;3(1):e000113.
Additional Infomation	AZD-8848 is under investigation in clinical trial NCT01818869 (To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses AZD8848 in Healthy Subjects).

Solubility Data

Solubility (In Vitro)

DMSO : ~25 mg/mL (~43.88 mM)

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. 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. 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 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	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.