RO1138452-CAY10441-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERO1138452Cat. No.: HY-108912CAS No.: 221529-58-4Synonyms: CAY10441分式: CHNO分量: 309.41作靶点: Prostaglandin Receptor作通路: GPCR/G Protein储存式: Pure form -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 33.33 mg

2、/mL (107.72 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.08 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (8.08 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIV

3、ITY物活性 RO1138452种有效的选择性前列环素 IP (prostacyclin) 受体拮抗剂。RO1138452 对 IP 受体具有的亲和。在板中，pKi 值为 9.30.1; 在重 组 IP 受体系统中，pKi 值为 8.70.06。IC50 & Target Rat I2 Receptor Rat I2 Receptor Rabbit PAF Receptor Human 2A7 nM (IC50) 8.33 (pKi) 52.9 nM (IC50) adrenoceptor724 nM (IC50)Rat 1B adrenoceptor Human Muscarinic M4

4、Human muscarinic M2 Human muscarinic M13280 nM (IC50) Receptor Receptor Receptor1450 nM (IC50) 2220 nM (IC50) 2570 nM (IC50)Human muscarinic M5 Rat 5-HT1B Receptor pig 5-HT2C Receptor Rat 5-HT2A ReceptorReceptor 1130 nM (IC50) 1190 nM (IC50) 3040 nM (IC50)3110 nM (IC50)Human 5-HT1A Guinea-pig 5-HT4

5、Rat 1B adrenoceptor Human 2AReceptor Receptor 5.87 (pKi) adrenoceptor8580 nM (IC50) 8910 nM (IC50) 6.49 (pKi)Human muscarinic M1 Human muscarinic M5 Human muscarinic M2 Human muscarinic M4Receptor Receptor Receptor Receptor5.66 (pKi) 5.81 (pKi) 5.88 (pKi) 6.14 (pKi)Rabbit PAF Receptor Guinea-pig 5-H

6、T4 Human 5-HT1A Rat 5-HT2A Receptor7.9 (pKi) Receptor Receptor 5.71 (pKi)5.35 (pKi) 5.37 (pKi)Rat 5-HT1B Receptor Pig 5-HT2C Receptor6.11 (pKi) 6.11 (pKi)体外研究 RO1138452 is IP receptor antagonist. The pIC50 values of RO1138452 in attenuating cAMP accumulation is7.00.07. Functional antagonism of RO113

7、8452 is studied by measuring inhibition of carbaprostacyclin-induced cAMP accumulation in CHO-K1 cells stably expressing the human IP receptor. The antagonistaffinity (pKi) of RO1138452 is 9.00.06. Selectivity profiles for RO1138452 are determined via a panel ofreceptor binding and enzyme assays. RO

8、1138452 displays affinity at imidazoline2 (I2) (8.3) and plateletactivating factor (PAF) (7.9) receptors 1. RO1138452 (10 pM-10 M) added to cells concurrently with a fixedconcentration of Taprostene (1 M) prevents, in a concentration-dependent manner, the inhibition of CXCL9and CXCL10 release, with

9、pA50 (molar) values of -8.730.11 and -8.470.16 (p0.05), respectively 2.体内研究RO1138452 is a potent and selective antagonist for both human and rat IP receptors and that is possessesanalgesic and anti-inflammatory potential. RO1138452 (1-10mg/kg, i.v.) significantly reduces acetic acid-induced abdomina

10、l constrictions. RO1138452 (3-100mg/kg, p.o.) significantly reduces carrageenan-induced2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEmechanical hyperalgesia and edema formation. Onehour after administration of RO1138452 (5mg/kg, i.v.) torats, the total plasma concentration is 0.189 g/mL, whereas

11、the free plasma concentrations is calculated tobe 0.009g/mL (28 nM) 1.PROTOCOLKinase Assay 1 Selectivity is determined by the ability of RO1138452 (10M) to displace specific binding of standardradioligands at 51 receptors. When significant displacement of radioligand is observed (70% forRO1138452),

12、complete concentration-dependent displacement curves (in triplicate) are constructed togenerate IC50 values. Displacement binding at the EP3 receptor is performed. Enzyme inhibition assays arealso conducted. RO1138452 is evaluated at 10M in triplicate for inhibition of COX isoforms: COX-1 (ramsemina

13、l vesicle), COX-2 (sheep placenta and human umbilical vein). Arachidonic acid is used as a substrateand PGE2 accumulation is detected 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 BEAS-2B cells are incubated for 30 min at 37C in supplem

14、ent-free keratinocyte serum-free medium (KSFM)in the absence and presence of 100 nM RO1138452. Cells are washed with supplement-free KSFM,incubated in the same medium for defined periods, and exposed to 1 M Taprostene. Four hours later, cellsare harvested in reporter lysis buffer, and luciferase act

15、ivity is measured. The viability HAECs and BEAS-2Bcells is determined colorimetrically by measuring the reduction of the tetrazolium salt MTT to formazan, bymitochondrial dehydrogenases 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Admi

16、nistration 1 Male Sprague-Dawley rats (n=3) are administered RO1138452 (5mg/kg, i.v.). At various times after doseadministration, the rats are anesthetized by halothane (5%), blood is collected by orbital bleed into aheparinized syringe and a plasma fraction is obtained by centrifugation of the bloo

17、d at 2600 g for 5min in aclinical centrifuge. The level of RO1138452 in each sample is determined by high-performance liquidchromatography with detection by mass spectrometry 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Bley KR, et al.

18、 RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptorantagonists. Br J Pharmacol. 2006 Feb;147(3):335-45.2. Ayer LM, et al. 4,5-Dihydro-1H-imidazol-2-yl)-4-(4-isopropoxy-benzyl)-phenyl-amine (RO1138452) is a selective, pseudo-irreversibleorthosteric antagonist at the prostacyclin (IP)-receptor expressed by human airway epithelial cells: IP-receptor-mediated inhibi