AM966

AM966 is an orally bioavailable, potent, and selective antagonist of the lysophosphatidic acid receptor 1 (LPA₁) that has an IC₅₀ value of 17 nM in a calcium assay using CHO cells transfected with the human LPA₁ receptor.¹ It is selective for LPA₁ over the LPA₂, LPA₃, LPA₄, and LPA₅ receptors (IC₅₀s = 1,700, 1,600, 7,700, and 8,600 nM for LPA_2-5, respectively). In vitro, AM966 inhibits LPA-induced lung fibroblast cell chemotaxis (IC₅₀ = 181 nM), increases barrier permeability, activates RhoA, and induces phosphorylation of myosin light chain and vascular endothelium cadherin (VE-cadherin).^2,3 At a dose of 30 mg/kg in mice, it reduces inflammation, tissue fibrosis, and vascular permeability following bleomycin-induced lung injury. AM966 also blocks amitriptyline-induced ERK1/2, CREB, and insulin growth factor-1 receptor (IGF-IR) phosphorylation in vitro.²

WARNING This product is not for human or veterinary use.

1. Swaney, J.S., Chapman, C., Correa, L.D., et al. A novel, orally active LPA₁ receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br. J. Pharmacol. 160(7), 1699-1713 (2010).

2. Olianas, M.C., Dedoni, S., and Onali, P. Antidepressants activate the lysophosphatidic acid receptor LPA₁ to induce insulin-like growth factor-I receptor transactivation, stimulation of ERK1/2 signaling and cell proliferation in CHO-K₁ fibroblasts. Biochem. Pharmacol. 95(4), 311-323 (2015).

3. Cai, J., Wei, J., Li, S., et al. AM966, an antagonist of lysophosphatidic acid Receptor 1, increases lung microvascular endothelial permeability through activation of Rho signaling pathway and phosphorylation of VE-cadherin. Mediators Inflamm. 2017, 6893560 (2017).