AM095

AM095 is an orally bioavailable antagonist of lysophosphatidic acid receptor 1 (LPA₁) with IC₅₀ values of 25 and 23 nM in CHO cells expressing human or mouse receptors, respectively.¹ It is selective for LPA₁ over LPA₂, LPA₃, LPA₄, and LPA₅ (IC₅₀s = >10,000 nM for human LPA_2-5). It inhibits chemotaxis of CHO cells overexpressing LPA₁ and of A2058 human melanoma cells (IC₅₀s = 778 and 233 nM, respectively) and prevents LPA-induced increases in plasma histamine levels in mice (ED₅₀ = 8.3 mg/kg).² It also decreases collagen and protein levels in bronchoalveolar lavage fluid (BALF) in a mouse model of bleomycin-induced lung injury (ED₅₀s = ~10 mg/kg for both) and decreases kidney fibrosis in a mouse model of unilateral ureteral obstruction when administered at a dose of 30 mg/kg for eight days.

WARNING This product is not for human or veterinary use.

1. Castelino, F.V., Seiders, J., Bain, G., et al. Genetic deletion or pharmacologic antagonism of LPA₁ ameliorates dermal fibrosis in a scleroderma mouse model. Arthritis Rheum. 63(5), 1405-1415 (2011).

2. Swaney, J.S., Chapman, C., Correa, L.D., et al. Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist. J. Pharmacol. Exp. Ther. 336(3), 693-700 (2011).