Brexpiprazole-OPC-34712-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBrexpiprazoleCat. No.: HY-15780CAS No.: 913611-97-9Synonyms: OPC-34712分式: CHNOS分量: 433.57作靶点: 5-HT Receptor; Dopamine Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C

2、1 month溶解性数据体外实验 DMSO : 48 mg/mL (110.71 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.3064 mL 11.5322 mL 23.0643 mL5 mM 0.4613 mL 2.3064 mL 4.6129 mL10 mM 0.2306 mL 1.1532 mL 2.3064 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

3、性 Brexpiprazole 5-HT1A 和多巴胺受体的部分激动剂，Ki分别为0.12 nM 和 0.3 nM。 Brexpiprazole也是5-HT2A 受体的拮抗剂，Ki 为0.47 nM。IC50 & Target Ki: 0.12 nM (5-HT1A), 0.3 nM (D2L), 0.47 nM (5-HT2A) 11/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 Brexpiprazole, a novel serotonin-dopamine activity modulator: A role for serot

4、onin 5-HT1A and 5-HT2Areceptors. Brexpiprazole also shows potent antagonist activity at human nor adrenergic 1B (Ki=0.17 nM)and 2C receptors (Ki=0.59 nM). Brexpiprazole significantly potentiates nerve growth factor (NGF)-inducedneurite outgrowth in PC12 cells, in a concentration dependent manner. Br

5、expiprazole (1 M) increases thenumber of cells with neurites in PC12 cells. Treatment with Brexpiprazole (0.001, 0.01, 0.1 or 1.0 M) inconjunction with NGF (2.5 ng/mL) increases the number of cells with neurites, in a concentration-dependentmanner 1.体内研究 Brexpiprazole (0.01, 0.03, 0.1 mg/kg, p.o.) s

6、ignificantly ameliorates dizocilpine-induced social recognitiondeficits, without sedation or a reduction of exploratory behavior. In addition, Brexpiprazole alone has no effecton social recognition in untreated controlmice. By contrast, neither Risperidone(0.03 mg/kg, p.o.) norOlanzapine (0.03 mg/kg

7、, p.o.) alters Dizocilpine induced social recognition deficits. Finally,the effect ofBrexpiprazole on Dizocilpine-induced social recognition deficits is antagonized by WAY-100,635. Theseresults suggest that Brexpiprazole can improve Dizocilpine-induced social recognition deficits via 5-HT1Areceptor

8、activation in mice 2.PROTOCOLCell Assay 1 PC12 cells are cultured at 37C, 5% CO2 in Dulbeccos modified Eagles medium (DMEM), supplementedwith 5% heat-inactivated fetal bovine serum (FBS),10% heat-inactivated horse serum, and 1% penicillin-streptomycin. Medium is changed two to three times a week. PC

9、12 cells are plated onto 24- well tissueculture plates coated with poly-D-lysine/laminin. Cells are plated at relatively low density (0.25104cells/cm2) in DMEM medium containing 0.5% FBS,1% penicillin-streptomyc in Medium containing a minimallevel of serum (0.5% FBS) is used. In this study, 2.5 ng/m

10、L of NGF is used to study the potentiating effects ofBrexpiprazole on neurite outgrowth. Twenty-four hours after plating, the medium is replaced with DMEMmedium containing 0.5% FBS and 1% penicillin-streptomycin with NGF (2.5 ng/mL), with or withoutBrexpiprazole (0.001,0.01,0.1 or 1 M), WAY-100,635

11、(5-HT1A receptor antagonist;10 M), raclopride(dopamine D2 receptor antagonist;10 M), DOI (5-HT2A receptor agonist;0.1,1 or 10 M), M100,907 (5-HT2A receptor antagonist; 0.1, 1 or 10 M), xestospongin C (IP3 receptor antagonist; 1 M), 2-APB (IP3receptor antagonist;100 M), fluoxetine (5-HT transporter i

12、nhibitor: 1 M), or paroxetine (5-HT transporterinhibitor: 1 M). Four days after incubation with NGF (2.5ng/mL) with or without specified drugs,morphometric analysis is performed on digitized images of live cells taken under phase-contrast illumination,with an inverted microscope linked to a camera.

13、Images of three fields per well are taken, with an average of100 cells per field. Differentiated cells are counted by visual examination of the field; only cells that had atleast one neurite with a length equal to the cell body diameter are counted, and are then expressed as apercentage of the total

14、 cells in the field. Counting is performed in ablinded manner 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Male C57BL/6NCrSlc mice aged between 4 and 5 weeks old are selected as stranger mice, while animalsbetween 8 an

15、d 10 weeks old are used for this study. All mice are housed in groups of five percage, in a roommaintained at 232C and 6010% humidity, with a 12/12h light/dark cycle (lights on at 7:00 a.m.).The miceare given free access to food and water. Brexpiprazole is dissolved in 5% (w/v) gum Arabic and admini

16、stered2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEorally (p.o.), at 10 mL/kg, 1 h prior to sociability testing. The doses of antipsychotic drugs are selected basedon doses that did not impact locomotion.MCE has not independently confirmed the accuracy of these methods. They are for reference on

17、ly.REFERENCES1. Ishima T, et al. Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin-dopamine activity modulator: a role for serotonin 5-HT1A and 5-HT2A receptors. Eur Neuropsychopharmacol. 2015 Apr;25(4):505-11.2. Yoshimi N, et al. Improvement of dizocilpine-induced social recognition deficits in mice by brexpiprazole, a novel serotonin-dopamineactivity