Biological Activity
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].
References
[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.
