AM966 - LPL Receptor Antagonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAM966Cat. No.: HY-15277CAS No.: 1228690-19-4分式: CHClNO分量: 490.93作靶點(diǎn): LPL Receptor作通路: GPCR/G Protein儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 105 mg/mL (213.88 mM)* means soluble, but

2、 saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.0370 mL 10.1848 mL 20.3695 mL5 mM 0.4074 mL 2.0370 mL 4.0739 mL10 mM 0.2037 mL 1.0185 mL 2.0370 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AM966種親和性的選擇性LPA1-拮抗劑，抑制LPA-刺激的細(xì)胞內(nèi)鈣釋放，IC50 為 17 nM。IC50 & Targ

3、et LPA1 1體外研究AM966 is a potent, selective, orally bioavailable LPA1 receptor antagonist. AM966 inhibits LPA1-mediatedchemotaxis of human A2058 melanoma cells (IC50=13843 nM), IMR-90 human lung fibroblasts1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE(IC50=18286 nM) and CHO mLPA1 cells (IC50=46954

4、 nM) 1. LPA-induced ERK1/2 activation iscompletely blocked by AM966 (100 nM), which selectively antagonizes LPA1 over LPA2-5, with an IC50value of 3.80.4 nM. Pre-treatment with AM966 (100 nM) completely blocks ERK1/2 phosphorylation inducedby either amitriptyline or mianserin 2.體內(nèi)研究 AM966 (30 mg/kg,

5、 BID) reduces vascular leakage, inflammation and lung injury and inflammation in a 3 daybleomycin model. AM966 inhibits lung fibrosis, maintains mouse body weight and decreases lunginflammation 14 days after bleomycin lung injury. AM966 reduces vascular leakage, tissue injury and pro-fibrotic cytoki

6、ne production in the 14 day bleomycin study. AM966 demonstrates greater efficacy compared topirfenidone in the 14 day bleomycin model. AM966 decreases mortality and fibrosis at late time points afterbleomycin injury 1.PROTOCOLCell Assay 2 CHO-K1 cells are grown to 80% confluency in 12-well plates, s

7、erum-starved for 24 h and incubated in serum-free medium with AM966. After 21 h, 3Hthymidine (0.5 Ci/well) is added and the incubation is continued for3 h. The medium is then removed, and the cells are placed on ice and washed twice with 1 mL of ice-coldPBS containing 5% trichloroacetic acid. Cells

8、are solubilized and 3Hthymidine incorporation is determinedby liquid scintillation counting. Assays are performed in triplicate 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 The oral exposure of AM966 is determined in f

9、asted mice. Animals received AM966 (10 mg/kg) in vehicle(water) by oral gavage and are then killed by CO2 inhalation at 1, 2, 4, 8 and 24 h post dose (n=2 animalsper time point for each test compound). Blood (approximately 300 L) is collected via cardiac puncture intoEDTA-containing tubes and centri

10、fuged at 1450g for 10 min. The plasma is removed and analysed forAM966 content by liquid chromatography-mass spectrometry (LCMS). Briefly, known amounts of AM966 areadded to thawed mouse plasma to yield a concentration range from 0.8 to 4000 ng/mL. Mouse plasmasamples are precipitated using acetonit

11、rile (1:4, v:v) containing the internal standard buspirone. A 10 Laliquot of the analyte mixture is injected using a Leap PAL autosampler. Analyses are performed using anAgilent Zorbax SB-C8 column (2.150 mm; 5 m) linked to a Shimadzu LC-10AD VP with SCL-10A VPsystem controller. Tandem mass spectrom

12、etric detection is carried out on a PE Sciex API3200 in the positiveion mode (ESI) by multiple reaction monitoring. The calibration curves are constructed by plotting the peak-area ratio of analysed peaks against known concentrations. The lower limit of quantitation is 0.8 ng/mL. Thedata are subject

13、ed to linear regression analysis with 1/x2weighting.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Neuropsychopharmacol Rep. 2019 Apr 25. J Clin Med. 2016 Jan 26;5(2). pii: E16. Biochem Pharmacol. 2015 Jun 15;95(4):311-23.2/3 Master of Smal

14、l Molecules 您邊的抑制劑師www.MedChemE J Biol Chem. 2016 Dec 30;291(53):27364-27370. Apoptosis. 2019 Jun;24(5-6):478-498.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. 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 receptortransactivation, stimulation of ERK1/2 signaling and cell proliferation in CHO-K1 fibroblasts. Biochem Pharmacol. 2