AM966 is a selective, potent and orally bioavailable antagonist of lysophosphatidic acid type 1 receptor (LPA1) with IC50 values of 17 and 19 nM for human or mouse LPA1, respectively [1]. Relative to LPA2, 3, 4, 5 receptors, AM966 shows 10-fold and 100-fold more selective in mouse and human cell lines for LPA1, respectively [1].
In vitro, AM966 shows to inhibit LPA-induced chemotaxis in IMR-90 human lung fibroblasts, A2058 human melanoma cells and CHO cells expressing LPA1 receptors [1].
In vivo, AM966 has been demonstrated to reduce total BALF cells, LDH activity, BALF collagen and total TGFβ concentrations in bleomycin-induced mice. Moreover, AM966 has been reported to block lung fibrosis, reduce lung inflammation and maintain body weight in mice induced by bleomycin [1].
Reference:
[1] Swaney JS1, Chapman C, Correa LD, Stebbins KJ, Bundey RA, Prodanovich PC, Fagan P, Baccei CS, Santini AM, Hutchinson JH, Seiders TJ,Parr TA, Prasit P, Evans JF, Lorrain DS. A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010 Aug;160(7):1699-713.