tcsc1129 AM095 (free acid)

AM095 (free acid) is a potent LPA1 receptor antagonist with IC₅₀ values of 0.98 and 0.73 μM for recombinant human or mouse LPA1 respectively.

IC50 & Target: IC50: 0.98 μM (human LPA1), 0.73 μM (mouse LPA1)

In Vitro: AM095 inhibits the LPA-induced calcium flux of CHO cells stably transfected with human or mouse LPA1. The IC₅₀ for AM095 antagonism of LPA-induced calcium flux of human or mouse LPA1-transfected CHO cells is 0.025 and 0.023 μM, respectively^[1]. AM095 reduces LPA-induced vasorelaxation by appr 90% at 10 μM as compared to vehicle control^[2]. AM095 inhibits LPA-driven chemotaxis of CHO cells overexpressing mouse LPA1 (IC₅₀=778 nM) and human A2058 melanoma cells (IC₅₀=233 nM)^[3].

In Vivo: Pharmacological antagonism of LPA1 with AM095 significantly attenuates bleomycin-induced dermal fibrosis^[1]. AM095 has high oral bioavailability and a moderate half-life and is well tolerated at the doses tested in rats and dogs after oral and intravenous dosing. AM095 dose-dependently reduces LPA-stimulated histamine release. AM095 attenuates bleomycin-induced increases in collagen, protein, and inflammatory cell infiltration in bronchalveolar lavage fluid. AM095 decreases kidney fibrosis in a mouse unilateral ureteral obstruction model^[3].