Darigabat
Based on 1 Customer Validation
Darigabat (PF-06372865) is an orally active, α2/α3/α5 subtype-selective GABAA positive allosteric modulator (PAM). Darigabat is a high affinity ligand at GABAA receptors containing α1/α2/α3/α5 subunits (Kis of 2.9 nM, 21 nM, 134 nM for α2, α1 PAM, α2 PAM, respectively), with low affinity for α4/α6 subunits. Darigabat can across the blood-brain barrier (BBB). Darigabat has anxiolytic activity and has the potential for epilepsy.
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- Pureza: 99.29%
- No. CAS: 1614245-70-3
- Fòrmula: C22H21FN4O3S
- Peso molecular:440.49
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Almacenamiento:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Ki: 2.9 nM (α2), 21 nM (α1 PAM) and 134 nM (α2 PAM)[1]
Darigabat (compound 34) has Ki values of 0.18 nM, 2.9 nM, 1.1 nM, 18 nM for human GABAA α1β3γ2, α2β2γ2, α3β3γ2, α5β2γ2 and 0.34 nM, 4.58 nM for rat GABAA α1β3γ2, α2β2γ2[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Darigabat (0.3, 3, 10 mg/kg for mouse and 1, 3, 10 mg/kg for rat; orally) exhibits efficacy in two models of epilepsy, PTZ induced seizures (mouse), and amygdala kindling (rat)[1].
Darigabat (0.1, 0.32, 1, 3.2 and 10 mg/kg; orally) has anxiolytic activity at 3.2 and 10 mg/kg in elevated plus maze (male C57Bl/6 mice)[1].
Darigabat has a T1/2 of 1.1 hours, a Clp of 22 mL/min/kg, and a Vss of 2.1 L/kg for rats[1].
Darigabat has a T1/2 of 0.9 hours, a Clp of 29 mL/min/kg, and a Vss of 3.4 L/kg for dogs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Chronic constriction injury (CCI) model (male Wistar rats)[1]
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Dosage:3, 10 mg/kg
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Administration:Orally
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Result:Significantly increased paw withdrawal latency.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 1614245-70-3
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Appearance Solid
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Peso molecular 440.49
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Fòrmula C22H21FN4O3S
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Color Off-white to yellow
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SMILES
CCN1C2=NN=CC(C(C=C3)=CC(C(C=CC([S](CC)(=O)=O)=C4)=C4OC)=C3F)=C2N=C1
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Synonyms
PF-06372865; CVL-865
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvente y solubilidad
DMSO : 50 mg/mL (113.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.68 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.68 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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.
Pureza y Documentación
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Ficha de datos (277 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2702 mL | 11.3510 mL | 22.7020 mL | 56.7550 mL |
| 5 mM | 0.4540 mL | 2.2702 mL | 4.5404 mL | 11.3510 mL | |
| 10 mM | 0.2270 mL | 1.1351 mL | 2.2702 mL | 5.6755 mL | |
| 15 mM | 0.1513 mL | 0.7567 mL | 1.5135 mL | 3.7837 mL | |
| 20 mM | 0.1135 mL | 0.5675 mL | 1.1351 mL | 2.8377 mL | |
| 25 mM | 0.0908 mL | 0.4540 mL | 0.9081 mL | 2.2702 mL | |
| 30 mM | 0.0757 mL | 0.3784 mL | 0.7567 mL | 1.8918 mL | |
| 40 mM | 0.0568 mL | 0.2838 mL | 0.5675 mL | 1.4189 mL | |
| 50 mM | 0.0454 mL | 0.2270 mL | 0.4540 mL | 1.1351 mL | |
| 60 mM | 0.0378 mL | 0.1892 mL | 0.3784 mL | 0.9459 mL | |
| 80 mM | 0.0284 mL | 0.1419 mL | 0.2838 mL | 0.7094 mL | |
| 100 mM | 0.0227 mL | 0.1135 mL | 0.2270 mL | 0.5675 mL |
Darigabat Related Classifications
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