Description
AZD-2098 (566203-88-1) is a potent, orally bioavailable antagonist of CCR4 (pIC50 = 7.8(h), 8.0(r), 8.0(m), 7.6(d)).1 Inactive at CXCR1/2, CCR1, CCR2b, CCR5, CCR7, and CCR8 @ 10 μM.
Uses
AZD-2098 is a potent and selective agonist of CCR4 chemokine receptor with IC50 values ranging from 10 to 25 nM across different species. CCR4 is involved in activation and migration of Th2 lymphocytes to the lungs in response to allergens. Treating sensitised rats results in reduced inflammation of lung tissue.
Biochem/physiol Actions
AZD-2098 is an orally active, potent and selective CCR4 antagonist (pIC50 = 7.8/8.0/8.0/7.6 against CCL22 binding to human/mouse/rat/dog CCR4; inactive toward CXCR1/2 & CCR1/2b/5/7/8 at 10 μM) with little or no activity toward a panel of ～120 receptors/enzymes. AZD-2098 effectively inhibits chemokine-induced cellular responses in vitro (pIC50 = 7.5 against CCL22-induced calcium influx in hCCR4-expressing CHO cells; pIC50 = 6.3 against CCL17- or CCL22-induced chemotaxis of primary human Th2 cells) and exhibits efficacy against antigen-induced inflammatory response among ovalbumin-sensitized rats in vivo (Emax = 7.5 μmol/kg p.o.; 1 h before and every 12 h after antigen challenge).
References
Kindon et al. (2017), Discovery of AZD-2098 and AZD-1678, Two Potent and Bioavailable CCR4 Receptor Antagonists; ACS Med. Chem. Lett. 8 981
