JNJ-42041935-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEJNJ-42041935Cat. No.: HY-12832CAS No.: 1193383-09-3分式: CHClFNO分量: 346.65作靶点: HIF/HIF Prolyl-Hydroxylase作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 36 mg/mL

2、 (103.85 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.8848 mL 14.4238 mL 28.8475 mL5 mM 0.5770 mL 2.8848 mL 5.7695 mL10 mM 0.2885 mL 1.4424 mL 2.8848 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 JNJ-42041935效的，竞争性和选择性的脯氨酰羟化酶P

3、HD抑制剂，抑制PHD1，PHD2 和 PHD3的pKi值分别为7.910.04，7.29 0.05和7.650.09。IC50 & Target pKi: 7.910.04 (PHD1), 7.29 0.05 (PHD2), 7.650.09(PHD3) 1体外研究JNJ-42041935 is the most potent inhibitor of PHD2181417 with a pIC50 value of 7.00.03. JNJ-420419351/2 Master of Small Molecules 您边的抑制剂师www.MedChemEalso inhibits full

4、-length PHD1, PHD2, andPHD3 enzymes (pKi values 7.910.04, 7.29 0.05, and 7.650.09,respectively) 1.体内研究 JNJ-42041935 is used to compare the effect of selective inhibition of PHD to intermittent, high doses (50 g/kg i.p.) of an exogenous erythropoietin receptor agonist in an inflammation induced anemi

5、a model in rats.JNJ-42041935 (100 mol/kg, once a day for 14 days) is effective in reversing inflammation induced anemia,whereas erythropoietin has no effect. Administration of JNJ-42041935 (100 mol/kg p.o.) for 5 consecutivedays resulted in a 2-fold increase in reticulocytes, an increase in hemoglob

6、in by 2.3 g/dl, and an increase inthe hematocrit of 9%. Two hours after oral administration of 300 mol/kg JNJ-42041935, thebioluminescence over the peritoneal area is increased by 2.2 0.3-fold relative to luciferase-treated vehiclecontrols in the mouse 1.PROTOCOLKinase Assay 1 The potency of JNJ-420

7、41935 for inhibition of the structurally related enzyme FIH is assessed by methodssimilar to those described for PHD2. In brief, activity of FIH is determined using purified glutathionetransferase-tagged full-length FIH amino acids 1 to 350 and a synthetic HIF-1 peptide corresponding toresidues Asp7

8、88 to Leu822. Compounds are preincubated with 17.1 nM FIH for 30 min, followed by a 10-minincubation with 1 M 2-14C2-oxoglutarate, in the presence of 10 M FeNH4SO4 in reaction buffer. Theselectivity of JNJ-42041935 for inhibition of a range of other targets available for testing in commercialassays

9、is also assessed at concentrations of 1 and 10 M 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: JNJ-42041935 is administered at doses of 30, 100, and 300 mol/kg to Balb/C mice . Plasma isAdministration 1 collected 6 h after the dose. Pla

10、sma erythropoietin concentration is measured. The hematological effects ofJNJ-42041935 are assessed by administering the 100 mol/kg dose on 5 consecutive days and collectingblood anticoagulated with EDTA on day 8 (3 days after the last dose) 1.MCE has not independently confirmed the accuracy of thes

11、e methods. They are for reference only.REFERENCES1. Barrett TD, et al. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylicacid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. 2011McePdfHeightCaution: Product has not