Bitopertin [845614-11-1]
Référence HY-10809-10mg
Conditionnement : 10mg
Marque : MedChemExpress
Bitopertin is a potent, noncompetitive glycine reuptake inhibitor, inhibits glycine uptake at human GlyT1 with a concentration exhibiting IC50 of 25 nM.
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Bitopertin Chemical Structure
CAS No. : 845614-11-1
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Based on 1 publication(s) in Google Scholar
Other Forms of Bitopertin:
- Bitopertin (R enantiomer) Obtenir un devis
Description |
Bitopertin is a potent, noncompetitive glycine reuptake inhibitor, inhibits glycine uptake at human GlyT1 with a concentration exhibiting IC50 of 25 nM. |
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IC50 & Target |
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In Vitro |
Bitopertin (RG1678) competitively blocks [3H]ORG24598 binding sites at human GlyT1b in membranes from Chinese hamster ovary cells. Bitopertin potently inhibits [3H]glycine uptake in cells stably expressing hGlyT1b and mGlyT1b, with IC50 values of 25±2 nM and 22±5 nM, respectively (n=6). Conversely, Bitopertin has no effect on hGlyT2-mediated glycine uptake up to 30 μM concentration. Bitopertin has high affinity for the recombinant hGlyT1b transporter. Under equilibrium conditions (1 h at room temperature), Bitopertin displaces [3H]ORG24598 binding with a Ki of 8.1 nM. In hippocampal CA1 pyramidal cells, Bitopertin enhances NMDA-dependent long-term potentiation at 100 nM but not at 300 nM[1]. Additional profiling revealed that Bitopertin (RG1678) has an excellent selectivity profile against the GlyT2 isoform (IC50>30 μM) and toward a panel of 86 targets including transmembrane and soluble receptors, enzymes, ion channels, and monoamine transporters (<41% inhibition at 10 μM is measured for all targets)[2]. MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. |
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In Vivo |
Bitopertin (RG1678) dose-dependently increases cerebrospinal fluid and striatal levels of glycine measured bymicrodialysis in rats. Additionally Bitopertin attenuates hyperlocomotion induced by the psychostimulant D-amphetamine or the NMDA receptor glycine site antagonist L-687,414 in mice. Bitopertin also prevents the hyper-response to D-amphetamine challenge in rats treated chronically with phencyclidine, an NMDA receptor open-channel blocker. Administration of vehicle has no effect on extracellular levels of striatal glycine, which remained constant throughout the experiment. In contrast, p.o. administration of Bitopertin (1-30 mg/kg) produced a dose-dependent increase in extracellular glycine levels. Bitopertin 30 mg/kg produces glycine levels 2.5 times higher than pretreatment levels. A similar dose-dependent increase in glycine concentration is observed in the CSF of rats treated p.o. with Bitopertin (1-10 mg/kg) compared with vehicle-treated animals, 3 h after drug administration. Interestingly, the level of CSF glycine increase 3 h after Bitopertin dosing is very similar to the increase in the microdialysis experiment at the same time point[1]. In vivo pharmacokinetic studies in rat and monkey reveals that Bitopertin (RG1678) has, in both species, a low plasma clearance, an intermediate volume of distribution, a good oral bioavailability (78% for rat, 56% for monkey), and a favorable terminal half-life (5.8 h for rat, 6.4 h for monkey). The plasma protein binding is high in the two preclinical species (97%) and in human (98%). The CNS penetration of Bitopertin in rat (brain/plasma=0.7) is better than that in mouse (brain/plasma=0.5)[2]. MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. |
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Essai clinique |
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Masse moléculaire |
543.46 |
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Formule |
C21H20F7N3O4S |
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CAS No. |
845614-11-1 |
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Appearance |
Solid |
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Color |
White to off-white |
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SMILES |
FC1=CC(C(F)(F)F)=CN=C1N2CCN(C(C3=CC(S(=O)(C)=O)=CC=C3O[C@H](C(F)(F)F)C)=O)CC2 |
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Livraison | Room temperature in continental US; may vary elsewhere. |
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Stockage |
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Solvant et solubilité |
In Vitro:
DMSO : ≥ 50 mg/mL (92.00 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) *"≥" means soluble, but saturation unknown. Preparing
Stock Solutions
View the Complete Stock Solution Preparation Table
*
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol) Concentration (start) × Volume (start) = Concentration (final) × Volume (final) This equation is commonly abbreviated as: C1V1 = C2V2 In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage mg/kgAnimal weight Dosing volume Number of animals Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO
+
%
+
%
Tween-80
+
%
Saline
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
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Pureté et documentation |
Purity: 99.59% |
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Références |
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Complete Stock Solution Preparation Table
*
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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DMSO | 1 mM | 1.8401 mL | 9.2003 mL | 18.4006 mL | 46.0015 mL |
5 mM | 0.3680 mL | 1.8401 mL | 3.6801 mL | 9.2003 mL | |
10 mM | 0.1840 mL | 0.9200 mL | 1.8401 mL | 4.6002 mL | |
15 mM | 0.1227 mL | 0.6134 mL | 1.2267 mL | 3.0668 mL | |
20 mM | 0.0920 mL | 0.4600 mL | 0.9200 mL | 2.3001 mL | |
25 mM | 0.0736 mL | 0.3680 mL | 0.7360 mL | 1.8401 mL | |
30 mM | 0.0613 mL | 0.3067 mL | 0.6134 mL | 1.5334 mL | |
40 mM | 0.0460 mL | 0.2300 mL | 0.4600 mL | 1.1500 mL | |
50 mM | 0.0368 mL | 0.1840 mL | 0.3680 mL | 0.9200 mL | |
60 mM | 0.0307 mL | 0.1533 mL | 0.3067 mL | 0.7667 mL | |
80 mM | 0.0230 mL | 0.1150 mL | 0.2300 mL | 0.5750 mL |