PF 04531083
Based on 1 Customer Validation
PF 04531083 is an orally active and selective NaV1.8 blocker with an IC50 of 0.7 μM. PF 04531083 is a blood-brain barrier (BBB) penetrant compound. PF 04531083 can be used for the research of respiratory system and neuropathic/inflammatory pain.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.62%
- No. CAS: 1079400-07-9
- Fòrmula: C17H16ClN5O2
- Peso molecular:357.79
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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Nav1.8 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
0.19 μM
Compound: 13
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Inhibition of human Nav1.8/beta1 expressed in HEK293 cells by manual patch clamp electrophysiology
Inhibition of human Nav1.8/beta1 expressed in HEK293 cells by manual patch clamp electrophysiology
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[PMID: 26101568] |
| HEK293 | IC50 |
0.7 μM
Compound: 13
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Inhibition of human Nav1.8 expressed in HEK293 cells assessed as reduction in blue fluorescent signal by VSP-FRET assay
Inhibition of human Nav1.8 expressed in HEK293 cells assessed as reduction in blue fluorescent signal by VSP-FRET assay
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[PMID: 26101568] |
| HEK293 | IC50 |
36 μM
Compound: 13
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Inhibition of human Nav1.7 expressed in HEK293 cells by FRET assay
Inhibition of human Nav1.7 expressed in HEK293 cells by FRET assay
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[PMID: 26101568] |
| HEK293 | IC50 |
37 μM
Compound: 13
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Inhibition of human Nav1.1 expressed in HEK293 cells by IonWorks Quattro selectivity assay
Inhibition of human Nav1.1 expressed in HEK293 cells by IonWorks Quattro selectivity assay
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[PMID: 26101568] |
| HEK293 | IC50 |
37 μM
Compound: 13
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Inhibition of human Nav1.5 expressed in HEK293 cells by IonWorks Quattro selectivity assay
Inhibition of human Nav1.5 expressed in HEK293 cells by IonWorks Quattro selectivity assay
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[PMID: 26101568] |
PF 04531083 (1 μM) stimulates baseline activity by ~50% and the firing response to 10% CO2 in chemosensitive retrotrapezoid nucleus (RTN) neuron in a slice from a Tcf4tr/+ mice[3].
PF 04531083 blocks human Nav1.8, hNav1.1, hNav1.5, hNav1.7, TTX-r rat DRG, TTX-R hDRG, hERG with IC50 values of 0.19, 37, 37, 36, 0.54, 0.2, >30 μM, respectively[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | Tmax | Clearance (CL) | Vd | Bioavailability |
|---|---|---|---|---|---|---|---|
| Rat | 1 mg/kg | i.v. | 3.9 h | - | 6.7 mL/min/kg | 2.25 L/kg | - |
| Rat | 2 mg/kg | p.o. | N.D. | 1.3 h | 11.4 mL/min/kg | - | 59 % |
PF 04531083 (40 mg/kg; 1.5 h) is efficacious in the tibial nerve transection (TNT) induced mechanical allodynia model in rat[2].
PF 04531083 inhibits native tetrodotoxin-resistant (TTX-R) currents in rodent dorsal root ganglion (DRG) neurons with an IC50 of 0.54 μM[2].
PF 04531083 (40 mg/kg; 1.5 h) improves baseline breathing in Tcf4tr/+ mice[3].
PF 04531083 (30 min before test) improves behavioral abnormalities associated with Pitt-Hopkins syndrome (PTHS) in Tcf4tr/+ mice[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Tcf4+/+ and Tcf4tr/+ mice [3]
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Dosage:40 mg/kg
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Administration:Intraperitoneal injection (i.p.), 1.5 h before test
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Result:Decreased episodes of hyperventilation, increased the occurrence of spontaneous sighs, diminished duration of post-sigh apnea and improved the CO2 minute ventilatory response in Tcf4tr/+ mice.
Showed stable respiratory activity in Tcf4+/+ mice.
Showed a robust increase in respiratory activity (62.5% increase in minute ventilation from 3 to 7% CO2) in Tcf4tr/+ pups.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 1079400-07-9
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Appearance Solid
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Peso molecular 357.79
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Fòrmula C17H16ClN5O2
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Color Light yellow to yellow
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SMILES
ClC1=CC=C(OC)C=C1C2=C(N=C(NC(C3=CC=NN3C)=O)C=C2)N
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 100 mg/mL (279.49 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. 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. 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: ≥ 2.08 mg/mL (5.81 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (5.81 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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.
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 (279 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Yekkirala AS, et al. Breaking barriers to novel analgesic drug development. Nat Rev Drug Discov. 2017 Aug;16(8):545-564. [Content Brief]
[2]. Bagal SK, et al. Discovery and Optimization of Selective Nav1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain. ACS Med Chem Lett. 2015 Apr 29;6(6):650-4. [Content Brief]
[3]. Cleary CM, et al. Disordered breathing in a Pitt-Hopkins syndrome model involves Phox2b-expressing parafacial neurons and aberrant Nav1.8 expression. Nat Commun. 2021 Oct 13;12(1):5962. [Content Brief]
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. 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 | 2.7949 mL | 13.9747 mL | 27.9494 mL | 69.8734 mL |
| 5 mM | 0.5590 mL | 2.7949 mL | 5.5899 mL | 13.9747 mL | |
| 10 mM | 0.2795 mL | 1.3975 mL | 2.7949 mL | 6.9873 mL | |
| 15 mM | 0.1863 mL | 0.9316 mL | 1.8633 mL | 4.6582 mL | |
| 20 mM | 0.1397 mL | 0.6987 mL | 1.3975 mL | 3.4937 mL | |
| 25 mM | 0.1118 mL | 0.5590 mL | 1.1180 mL | 2.7949 mL | |
| 30 mM | 0.0932 mL | 0.4658 mL | 0.9316 mL | 2.3291 mL | |
| 40 mM | 0.0699 mL | 0.3494 mL | 0.6987 mL | 1.7468 mL | |
| 50 mM | 0.0559 mL | 0.2795 mL | 0.5590 mL | 1.3975 mL | |
| 60 mM | 0.0466 mL | 0.2329 mL | 0.4658 mL | 1.1646 mL | |
| 80 mM | 0.0349 mL | 0.1747 mL | 0.3494 mL | 0.8734 mL | |
| 100 mM | 0.0279 mL | 0.1397 mL | 0.2795 mL | 0.6987 mL |
PF 04531083 Related Classifications
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