AM966 is a potent, selective, orally bioavailable antagonist of the LPA1 receptor. It effectively inhibits LPA1-mediated chemotaxis in various cell types, including human A2058 melanoma cells (IC50=138±43 nM), IMR-90 human lung fibroblasts (IC50=182±86 nM), and CHO mLPA1 cells (IC50=469±54 nM) [1]. LPA-induced activation of ERK1/2 is entirely suppressed by AM966 (100 nM), which exhibits selective antagonism against LPA1 receptor over LPA2-5, with an IC50 value of 3.8±0.4 nM. Pretreatment with AM966 (100 nM) completely abolishes ERK1/2 phosphorylation induced by Mianserin [2].
体内研究
In a Bleomycin model lasting 3 days, AM966 (30 mg/kg, BID) mitigates vascular leakage, inflammation, and lung injury. Additionally, it inhibits lung fibrosis, maintains mouse body weight, and reduces lung inflammation 14 days post-Bleomycin lung injury. AM966 demonstrates superior efficacy compared to Pirfenidone in the 14-day Bleomycin model, reducing mortality and fibrosis at later time points following Bleomycin injury [1].
体外研究
AM966 is a potent, selective, orally bioavailable antagonist of the LPA1 receptor. It effectively inhibits LPA1-mediated chemotaxis in various cell types, including human A2058 melanoma cells (IC50=138±43 nM), IMR-90 human lung fibroblasts (IC50=182±86 nM), and CHO mLPA1 cells (IC50=469±54 nM) [1].
LPA-induced activation of ERK1/2 is entirely suppressed by AM966 (100 nM), which exhibits selective antagonism against LPA1 receptor over LPA2-5, with an IC50 value of 3.8±0.4 nM. Pretreatment with AM966 (100 nM) completely abolishes ERK1/2 phosphorylation induced by Mianserin [2].
作用机制
AM966 can antagonize LPA1 receptors and inhibit LPA-stimulated intracellular calcium release.[1]
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