RG3039
Based on 3 publication(s) in Google Scholar
RG3039 (PF-06687859) is an orally active, blood-brain barrier-permeable DcpS inhibitor with an IC50 of 4.2 nM against hDcpS. RG3039 inhibits the decapping activity of DcpS and maintains DcpS in a catalytically inactive conformation in the central nervous system and other tissues. RG3039 extends survival and improves function in spinal muscular atrophy mice. RG3039 is applicable to research related to spinal muscular atrophy.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit: 99.30%
- CAS. Nr.: 1005504-62-0
- Formel: C21H23Cl2N5O
- Molecular Weight:432.35
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Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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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Publications Citing Use of MedChemExpress (MCE) RG3039
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Biologische Aktivität
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DcpS |
RG3039 (1-100 nM) potently inhibits the decapping enzyme activity of purified hDcpS, with an IC50 of 4.2 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
RG3039 (20 mg/kg; p.o.; once daily; postnatal day 11 to postnatal day 20) confers only a very weak survival benefit in 2B/2 SMA mice (median survival time: 23 days)[1].
RG3039 (3-40 mg/kg; daily; starting from postnatal day 1) hydrochloride potently inhibits DcpS in vivo, and improves survival rate, motor function, synaptic connectivity, neuromuscular junction function and muscle size in severe SMA mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:FVB/N (neonatal pups; hemizygous SMA, generated by crossing FVB.Cg-Tg(SMN2)2HungSmn1tm1Hung/J 5058 mice)[1]
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Dosage:20 mg/kg
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Administration:p.o.; once daily; P4 to P11
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Result:Increased median survival by 38% compared with vehicle-treated mice.
Maintained righting reflex times of 10-14 s until P11, whereas vehicle-treated mice showed progressive slowing of righting reflex from ~13 s at P6 to 41 s at P10.
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Animal Model:SMAD7 (severe spinal muscular atrophy delta 7) on FVB background (postnatal day 1, SMA model: null for endogenous mouse Smn gene, expressing human SMN2 gene and delta 7 transgene)[2]
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Dosage:10 mg/kg (survival, motor function, molecular/histological/electrophysiological endpoints); 3 mg/kg (DcpS inhibition); 20 mg/kg; 40 mg/kg (toxicity)
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Administration:daily; from postnatal day 1 (until death for 10,20,40 mg/kg; to P10 for 3 mg/kg)
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Result:Increased median survival by 26% compared with vehicle-treated mice.
Increased maximal weight achieved by 16%.
Improved righting time latencies after P11.
Improved ambulatory index scores between P13 and P17.
Increased full-length SMN transcript levels by 30-40% in neural tissues (spinal cord, brain) at P10, 6 hours after the last dose.
Increased VGLUT1 synapses on L3-L5 motor neurons by 50% at P13.
Increased percentage of fully innervated neuromuscular junctions (NMJs) to 57.4% in SPI muscle and 40.6% in longissimus capitis muscle at P12-P13.
Increased endplate potential (EPP) amplitude and quantal content by 30% in EDL muscle at P12-P13.
Decreased percentage of silent NMJs in splenius muscle to 20% at P12-P13.
Increased longissimus capitis muscle cross-sectional area by 80% and individual myofiber size by 95% at P12.
Inhibited DcpS enzyme activity by 90% within 2 hours and remained 80% inhibited 72 hours after the last dose in brain tissue (3 and 10 mg/kg doses dosed to P10).
Caused impaired weight gain and shortened survival (40 mg/kg dose).
Chemical Information
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CAS. Nr. 1005504-62-0
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Appearance Solid
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Molecular Weight 432.35
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Formel C21H23Cl2N5O
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Color White to off-white
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SMILES
NC1=NC(N)=C2C(OCC3CCN(CC4=C(Cl)C=CC=C4Cl)CC3)=CC=CC2=N1
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Synonyms
PF-06687859
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (3)
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Journal Impact Factor
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Most Recent
Lösungsmittel & Löslichkeit
DMSO : 5 mg/mL (11.56 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : < 0.1 mg/mL (insoluble)
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.
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.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Reinheit & Dokumentation
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Data Sheet (280 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Gogliotti RG, et al. The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models. Hum Mol Genet. 2013 Oct 15;22(20):4084-101. [Content Brief]
[2]. Van Meerbeke J, et al. The DcpS inhibitor RG3039 improves motor function in SMA mice. Hum Mol Genet. 2013 Oct 15;22(20):4074-83. [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, 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3129 mL | 11.5647 mL | 23.1294 mL | 57.8235 mL |
| 5 mM | 0.4626 mL | 2.3129 mL | 4.6259 mL | 11.5647 mL | |
| 10 mM | 0.2313 mL | 1.1565 mL | 2.3129 mL | 5.7824 mL |
RG3039 Related Classifications
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