AM966 是一种具有优异亲和力的特异性口服 LPA1 拮抗剂,可抑制 LPA 刺激的细胞内钙释放,IC50为 17 nM。
产品描述
AM966, a excellent affinity, specific, oral LPA1(IC50=17 nM) antagonist, suppresses LPA-stimulated intracellular calcium release.
体外活性
Pre-treatment with AM966 (100 nM) completely blocks ERK1/2 phosphorylation induced by either amitriptyline or mianserin. LPA-induced ERK1/2 activation is completely blocked by AM966 (100 nM), which selectively antagonizes LPA1 over LPA2-5, with an IC50 value of 3.8±0.4 nM. 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 mLPA1 cells (IC50=469±54 nM).
体内活性
In a 3-day bleomycin model, AM966 (30 mg/kg, BID) reduces vascular leakage, inflammation and lung injury and inflammation.
细胞实验
AM966 (Chem Scene, Monmouth Junction, NJ, USA) is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO 0.5%) before use.CHO-K1 cells are grown to 80% confluency in 12-well plates, serum-starved for 24 h and incubated in serum-free medium with AM966. After 21 h, [3H]thymidine (0.5 μCi/well) is added and the incubation is continued for 3 h. The medium is then removed, and the cells are placed on ice and washed twice with 1 mL of ice-cold PBS containing 5% trichloroacetic acid. Cells are solubilized and [3H]thymidine incorporation is determined by liquid scintillation counting. Assays are performed in triplicate.
动物实验
In fasted mice, received AM966 (10 mg/kg), which is prepared in water, by oral gavage.
Cas No.
1228690-19-4
分子式
C27H23ClN2O5
分子量
490.94
别名
4'-[4-[[[(1R)-1-(2-氯苯基)乙氧基]羰基]氨基]-3-甲基-5-异恶唑基]-联苯-4-乙酸
储存和溶解度
DMSO:105 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years