"目录号: HY-15277
GPCR/G Protein-
AM966 是一种高亲和性的选择性LPA1-拮抗剂，抑制LPA-刺激的细胞内钙释放，IC50为 17 nM。
LPL Receptor
相关产品
Siponimod-AM095-Ki16425-Ozanimod-LPA2 antagonist 1-BMS-986020-Ponesimod-TY-52156-Amiselimod hydrochloride-Etrasimod-S1p receptor agonist 1-Cenerimod-S1P1 Agonist III-CYM-5541-ONO-7300243-
生物活性
Description
AM966 is a high affinity, selective, oralLPA1-antagonist, inhibits LPA-stimulated intracellular calcium release (IC50=17 nM).
IC50& Target
LPA1[1]
In Vitro
AM966 is a potent, selective, orally bioavailable LPA1receptor antagonist. AM966 inhibits LPA1-mediated chemotaxis of human A2058 melanoma cells (IC50=138±43 nM), IMR-90 human lung fibroblasts (IC50=182±86 nM) and CHO mLPA1cells (IC50=469±54 nM)[1]. LPA-induced ERK1/2 activation is completely blocked by AM966 (100 nM), which selectively antagonizes LPA1over LPA2-5, with an IC50value of 3.8±0.4 nM. Pre-treatment with AM966 (100 nM) completely blocks ERK1/2 phosphorylation induced by either amitriptyline or mianserin[2].
In Vivo
AM966 (30 mg/kg, BID) reduces vascular leakage, inflammation and lung injury and inflammation in a 3 day bleomycin model. AM966 inhibits lung fibrosis, maintains mouse body weight and decreases lung inflammation 14 days after bleomycin lung injury. AM966 reduces vascular leakage, tissue injury and pro-fibrotic cytokine production in the 14 day bleomycin study. AM966 demonstrates greater efficacy compared to pirfenidone in the 14 day bleomycin model. AM966 decreases mortality and fibrosis at late time points after bleomycin injury[1].
References
[1].Swaney, JS, et al. A novel, orally active LPA1 receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010 Aug;160(7):1699-713.
[2].Olianas MC, et al. Antidepressants activate the lysophosphatidic acid receptor LPA(1) to induce insulin-like growth factor-I receptor transactivation, stimulation of ERK1/2 signaling and cell proliferation in CHO-K1 fibroblasts. Biochem Pharmacol. 2015 Ju