Laropiprant-MK-0524-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELaropiprantCat. No.: HY-50175CAS No.: 571170-77-9Synonyms: MK-0524分式: CHClFNOS分量: 435.9作靶點(diǎn): Prostaglandin Receptor作通路: GPCR/G Protein儲存式: 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 : 100 mg/m

2、L (229.41 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.74 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.74 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Laropiprant種有效的，選擇性的 DP receptor 拮抗劑，Ki 值為 0.57

3、 nM，對 TP 受體的 Ki 值為 2.95 nM。IC50 & Target DP/DP1 Receptor TP Receptor0.57 nM (Ki) 2.95 nM (Ki)體外研究 Laropiprant is a potent, selective DP receptor antagonist with Ki values of 0.57 nM and 2.95 nM for DPreceptor and TP Receptor, respectively. 1. Laropiprant (1 M) causes a significant inhibition of thea

4、ggregation but still counteractes the pronounced inhibition caused by PGD2 (30 nM) and BW245c (3 nM).Laropiprant blocks DP receptor-dependent increase in VASP phosphorylation, as well as inhibition of P-selectin expression, GPIIb/IIIa activation and in vitro thrombus formation. Laropiprant antagoniz

5、es theincreased platelet aggregation by TP and EP3 receptor activation. Laropiprant (10 M) and niacin inhibit invitro thrombus formation 2.PROTOCOLCell Assay 2 Vena8Fluoro+ Biochips are coated with collagen (200 g/mL) at 4C overnight and thereafter blocked withbovine serum albumin (10 g/mL) for 30 m

6、inutes at room temperature followed by washing steps. Wholeblood collected in sodium citrate is incubated with 3, 3-dihexyloxacarbocyanine iodide (1 M) in the dark for10 minutes. PGD2 (30 nM), BW245c (3 nM) are added 10 min before the start of perfusion, and the DPantagonist BWA868c or Laropiprant (

7、1 M) are added 10 min before the agonists. In another set ofexperiments whole blood is treated with niacin (3 mM), acetylsalicylic acid (1 mM) or Laropiprant (1 M and10 M) for 30 min. CaCl2 at a final concentration of 1 mM is added 2 minutes before the perfusion over thecollagen-coated chip. Perfusi

8、on is carried out at a shear rate of 30 dynes cm2. Thrombus formation isrecorded. Computerized image analysis is performed by DucoCell analysis software, where the area coveredby the thrombus is calculated. Data are expressed as percent of area covered in a control sample 2.MCE has not independently

9、 confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Sturino CF, et al. Discovery of a potent and selective prostaglandin D2 receptor antagonist, (3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopentabindol-3-yl-acetic acid (MK-0524). J Med Chem. 2007 Feb 22;50(4):794-806.2. Philipose S, et al. Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation. PLoS One.2012;7(8):e40222.McePdfHeightCaution: Product has not been fully validated f