| Description: |
AM211 is a potent, selective and orally bioavailable prostaglandin D2 (PGD2) receptor type 2 (DP2) antagonist, with IC50s of 4.9 nM, 7.8 nM, 4.9 nM, 10.4 nM for human, mouse, guinea pig, and rat DP2, respectively. |
| Target: |
AM211 is a potent, selective and orally bioavailable prostaglandin D2 (PGD2) receptor type 2 (DP2) antagonist, with IC50s of 4.9 nM, 7.8 nM, 4.9 nM, 10.4 nM for human, mouse, guinea pig, and rat DP2, respectively. |
| In Vivo: |
AM211 (1, 10, and 30 mg/kg, p.o.) dose-dependently decreases in the number of DK-PGD2-induced peripheral blood leukocytes, with a calculated ED50 of 0.85 mg/kg. AM211 (30 mg/kg) also decreases antigen-induced pulmonary inflammation in guinea pigs. AM211 (10 mg/kg, p.o.) causes significant decrease in ovalbumin (OVA)-induced sneezing in a mouse model of allergic rhinitis[1]. |
| In Vitro: |
AM211 is a potent, selective and orally bioavailable prostaglandin D2 (PGD2) receptor type 2 (DP2) antagonist, with IC50s of 4.9 nM, 7.8 nM, 4.9 nM, 10.4 nM for human, mouse, guinea pig, and rat DP2, respectively. In the presence of 0.2% serum albumin, AM211 inhibits radiolabeled PGD2 binding to human, mouse, guinea pig, and rat DP2 with IC50 values of 12.2, 20.1, 22.9, and 34.2 nM, respectively. AM211 displays high selectivity for DP2 versus other receptors in the prostanoid family, with IC50 values for the inhibition of radioligand binding to human TP, IP, DP1, and FP of more than 100 μM. AM211 (100 μM) shows no activity at COX-1, COX-2 enzymes as well as PPAR family of nuclear receptors[1]. |
| Animal Administration: |
Mice[1] In brief, mice are immunized by an intraperitoneal injection of 10 μg of ovalbumin (OVA) complexed with Imject Alum in a volume of 0.2 mL on days 1 and 8. Seven days later (day 15) mice are challenged intranasally with 20 μL of a 10 mg/mL solution of OVA. The challenge period occurs daily from days 15 to 19. Mice (seven/group) are randomLy assigned to receive either compound (AM211, 10 mg/kg) or vehicle (methyl cellulose, 10 mL/kg) and treated by oral gavage 1 h before each OVA challenge. The number of sneezes are counted for 8 min immediately after the OVA challenge on days 15, 17, and 19 by an independent observer who is blinded to the treatment groups[1]. |
| References: |
[1]. Bain G, et al. Pharmacology of AM211, a potent and selective prostaglandin D2 receptor type 2 antagonist that is active in animal models of allergic inflammation. J Pharmacol Exp Ther. 2011 Jul;338(1):290-301. |
