AZD8848

AZD8848 is a selective toll-like receptor 7 (TLR7) antedrug agonist which is developed for the research of asthma and allergic rhinitis[1].

Signaling Pathways >> Immunology/Inflammation >> Toll-like Receptor (TLR)

Research Areas >> Inflammation/Immunology

TLR7[1]

AZD8848 shows good activity against TLR7, with cellular pEC50s of 7.0 and 6.6 for human TLR7 and rat TLR7, respectively[1]. AZD8848 has an EC50 of 4 nM in the induction of IFNα from human PBMCs and an IC50 of 0.2-1.0 nM for the inhibition of IL-5, irrespective of whether the T cells have been polyclonally stimulated with PHA or via antigen presentation[1]. AZD8848 is a potent, selective TLR7 agonist antedrug able to inhibit Th2 responses in vitro[1]. AZD8848 has no activity against human TLR8 or against any of the other human TLRs[1].

AZD8848 (0.1-1 mg/kg; intratracheal) has a good pharmacokinetics in the Brown Norway rat[1]. AZD8848 (0.3 mg/kg; Intratracheal) suppresses the ovalbumin (OVA) challenge in the rat allergy model[1]. Animal Model: Brown Norway rat allergy model[1] Dosage: 0.1 mg/kg, 1 mg/kg Administration: Intratracheal (24 hours prior to and 24 hours after the OVA challenge) Result: Suppressed OVA challenge in a dose-dependent manner. Animal Model: Brown Norway rat[1] Dosage: 0.3 mg/kg (Pharmacokinetic Analysis) Administration: Intratracheal Result: Has a very short half-life (0.2 min) in rat blood and declined slowly after this point and levels above 1000 nmol/kg were maintained for over 5 hours.

[1]. Delaney S, et al. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848. BMJ Open Respir Res. 2016 Feb 23;3(1):e000113.