Basimglurant-RG7090-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBasimglurantCat. No.: HY-15446CAS No.: 802906-73-6Synonyms: RG7090; CTEP Derivative分式: CHClFN分量: 325.77作靶點: mGluR作通路: GPCR/G Protein; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體

2、外實驗 DMSO : 33.33 mg/mL (102.31 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.67 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (7.67 mM); Suspended solution; Need ultrasonic and warming3.

3、 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.67 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Basimglurant (RG7090)效，選擇性有服活性的mGlu5負(fù)變構(gòu)調(diào)節(jié)劑，Kd值為1.1 nM。IC50 & Target Kd: 1.1 nM (mGlu5) 1體外研究 3H-basimglurant saturation analysis on recombinant human mGlu5 reveals monophasic saturationisotherms wi

4、th Kd of 1.1 nM. In competition binding experiments on human recombinant mGlu5,Basimglurant (RG7090) fully displaces 3H-MPEP with a Ki of 35.6 nM and 3H-ABP688 with a Ki of 1.4 nM.In HEK293 cells stably expressing human mGlu5, Basimglurant (RG7090) inhibits quisqualate induced Ca2+mobilization with

5、an IC50 of 7.0 nM and 3H-inositolphosphate accumulation with an IC50 of 5.9 nM.Basimglurant (RG7090) shows similar potencies in radioligand binding and functional assay on human androdent mGlu5 receptor orthologues 1.體內(nèi)研究 Basimglurant (RG7090) is a potent, selective, and safe mGlu5 inhibitor with go

6、od oral bioavailability and longhalf-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It hasantidepressant properties which are corroborated by its functional magnetic imaging (fMRI) profile, as well asanxiolytic-like and antinociceptive features 1. It

7、is currently in phase II clinical studies for the treatment ofdepression and fragile X syndrome. In the Vogel conflict drinking test, Basimglurant dose dependentlyincreases the drinking time. The total plasma exposure of efficacious doses of Basimglurant (RG7090)ranges from 5 ng/mL (0.03 mg/kg) to 3

8、7 ng/mL (0.3 mg/kg) 2.PROTOCOLAnimal Rats: For intravenous PK, Basimglurant (RG7090) is formulated in N-methyl-pyrollidone (NMP)/salineAdministration 1 (30%/70%) as vehicle and administered at a volume of 2 mL/kg. For oral gavage (p.o.) the compound isadministered as suspension using gelatine/saline

9、 (7.5%/0.62% in water) at an administration volume of 4mL/kg 1.Monkey: For intravenous PK, Basimglurant (RG7090) is formulated in cyclodextrin solution as vehicle andadministered at a volume of 2 mL/kg. For oral gavage (p.o.), the compound is administered in capsule (2 mgin size-2 capsules, i.e. 0.3

10、 mg/kg) to fasted or fed monkeys in a cross-over design 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lindemann L, et al. Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negativeallosteric mo

11、dulator in clinical development for depression. J Pharmacol Exp Ther. 2015 Apr;353(1):213-33.2. Jaeschke G, et al. Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-1-(4-fluorophenyl)-2,5-2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEdimethyl-1H-imidazol-4-ylethynylpyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases.McePdfHeightCaution: Product has