Rosiptor-AQX-1125-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERosiptorCat. No.: HY-109011CAS No.: 782487-28-9Synonyms: AQX-1125分式: CHNO分量: 321.5作靶點(diǎn): Phosphatase作通路: Metabolic Enzyme/Protease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 : 150 mg/mL (46

2、6.56 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.1104 mL 15.5521 mL 31.1042 mL5 mM 0.6221 mL 3.1104 mL 6.2208 mL10 mM 0.3110 mL 1.5552 mL 3.1104 mL請(qǐng)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(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Rosiptor種分 SH2-containing inositol-5-phosphat

3、ase 1 (SHIP1) 的激活劑。IC50 & Target SHIP1 1體外研究Rosiptor is a small-molecule SHIP1 activator.The activating effect of Rosiptor on SHIP1 is 28% at 100 M inthe native enzyme but no effect of Rosiptor is observed when the SHIP1C2 enzyme is used. Rosiptor1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEindu

4、ces a concentration-dependent decrease in Akt phosphorylation in MOLT-4 cells, while it fails to affectAkt phosphorylation in Jurkat cells. At 0.1 M Rosiptor the inhibition amounts to an average of 34%, while at10 M the inhibition amounts to an average of 82% in two independent experiments. Rosiptor

5、 also induces aconcentration-dependent decrease in the production of multiple pro-inflammatory mediators in this system,without affecting cell viability. Rosiptor dose dependently inhibits chemotaxis of most cell types at lowmicromolar concentrations independent of the chemotactic stimulus 1.體內(nèi)研究 In

6、 female Sprague-Dawley rats, the single-dose pharmacokinetics of Rosiptor show that the increases inmaximal plasma concentration (Cmax) and AUC0- are dose-proportional at the lower end of the dosingregimen and greater than dose proportional at the higher doses. The oral bioavailability of Rosiptor i

7、n rats is66 and 85% at 10 and 30 mg/kg respectively. Oral bioavailability of Rosiptor in dogs is 88 and 104% at 10and 30 mg/kg respectively. High tissue concentrations of Rosiptor are detected, as compared to plasmaconcentrations, at each time point studied 1.PROTOCOLKinase Assay 1 To study enzyme k

8、inetics using either IP4 or diC8-PI(3,4,5)P3 (diC8-PIP3) as substrates, enzyme activityover time is measured in the absence or presence of Rosiptor and varying concentrations of IP4 or diC8-PIP3. Phosphate released at each substrate concentration is plotted against time, and initial velocities arede

9、termined and plotted against IP4 or diC8-PIP3 concentration 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Bone marrow cells are obtained from 4- to 8-week-old SHIP1+/+ and SHIP1-/- mice and bone marrow-derived mast cells (BMMCs) are pre

10、pared. Mast cells are sensitized overnight with anti-DNP IgE (SPE-7).Cells are then washed and incubated in the presence of vehicle control (media only) or Rosiptor (60 M) priorto stimulation with the indicated concentration of DNP-human serum albumin (DNP-HSA), followed by themeasurement of -hexosa

11、minidase from the culture supernatant 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Female Sprague-Dawley rats and beagle dogs (male and female) are treated with Rosiptor in saline by bolusAdministration 1 i.v. injection (at 1 mL/kg ) or by o

12、ral gavage (at 5 mL/kg). Blood is sampled 0 to 48 h post-dose and plasmaisolated. Plasma concentrations of Rosiptor are quantified using a validated HPLC-MS/MS method.Pharmacokinetic parameters are determined by non-compartmental analysis 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Stenton GR, et al. Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 1. Effects on inflammatory cell activation andchemotaxis in vitro and pharmacokinetic characterization in vivo. Br J Pharmacol. 2013 Mar;168(6):1506-18.McePdfH