BIIE-0246-AR-H-053591-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBIIE-0246Cat. No.: HY-101986CAS No.: 246146-55-4Synonyms: AR-H 053591分式: CHNO分量: 896.05作靶点: Neuropeptide Y Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数

2、据体外实验 DMSO : 100 mg/mL (111.60 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.1160 mL 5.5800 mL 11.1601 mL5 mM 0.2232 mL 1.1160 mL 2.2320 mL10 mM 0.1116 mL 0.5580 mL 1.1160 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。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结

3、果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (2.79 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 (2.79 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% co

4、rn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (2.79 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BIIE-0246种有效的、肽神经肽 Y (NPY) Y2 受体的度选择性拮抗剂，其 IC50 值为 15 nM。IC50 & Target NPYY2 receptor153 nM (IC50)体外研究 Receptor binding assays in HEK 293 cells transfected with the rat Y2 rec

5、eptor cDNA demonstrate that BIIE-0246 competes with high affinity (IC50=153 nM) against specific 125IPYY3-36 binding sites. In contrast,BIIE-0246, at concentrations up to 10 M, fails to compete for significant amounts of specific125IGR231118, 125IhPP and 125ILeu31, Pro34PYY binding sites in HEK 293

6、cells transfected with therat Y1, Y4 or Y5 receptor cDNA, respectively 1.体内研究 On chow diet, genetically obese NPY mice show increased gain in body weight and adiposity. Treatment withBIIE-0246 promotes body weight gain in both genotypes after 4.5 weeks, and already at 2 weeks. BIIE-0246has no signif

7、icant effect on fat mass gain. In DIO, BIIE-0246 has different effects on body weight andcomposition depending on the genotype (treatmentgenotype interaction in body weight Ppost hoc analysisreveals increased body weight and fat mass gain, and a tendency to decrease lean mass gain. In DIO-NPY,BIIE-0

8、246 inhibits fat mass gain (P=0.05). Interestingly, increased cholesterol levels are detected also in WTmice treated with BIIE-0246 for 2 weeks, but not in the 4.5-week cohort. In DIO-NPY mice in both treatmentgroups, cholesterol levels correlate positively with body fat mass (DIO-NPY vehicle P 2.PR

9、OTOCOLAnimal Mice 2Administration 2 Homozygous transgenic male OE-NPYDbH and WT mice are used. The mice are housed at 213C with a12-h light/12-h dark cycle. To study the effect of Y2-receptor antagonism in healthy conditions, standardrodent chow is fed ad libitum to OE-NPYDbH (NPY) and WT mice. To s

10、tudy the effect in DIO, western diet isfed for 8 weeks prior to the drug administration. Drug treatment is studied at the age of 20 weeks. Prior totreatments the mice are habituated for 2 weeks to the handling stress with daily saline injections (i.p). Micereceive 1.3 mg/kg of Y2-receptor antagonist

11、 (BIIE-0246) or vehicle with daily IP injections. At termination,mice are fasted for 3 h and blood glucose is measured from awake animals. Mice are then anesthetized withketamine (75 mg/kg i.p) and medetomidine (1 mg/kg i.p). Subcutaneous, epididymal, retroperitoneal andmesenteric white adipose tiss

12、ue (WAT) pads, interscapular brown adipose tissue (BAT) and liver arecollected and weighed 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Dumont Y, et al. BIIE0246, a potent and highly selective non-peptide neuropeptide Y Y(2) receptor a

13、ntagonist. Br J Pharmacol. 20002/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMar;129(6):1075-88.2. Liisa Ailanen, et al. Peripherally Administered Y2-Receptor Antagonist BIIE0246 Prevents Diet-Induced Obesity in Mice With ExcessNeuropeptide Y, but Enhances Obesity in Control Mice. Front Pharmacol. 2018; 9: 319.McePdf