RG3039 hydrochloride
Based on 1 Customer Validation
RG3039 hydrochloride is an orally active, blood-brain barrier-permeable DcpS inhibitor with an IC50 of 4.2 nM against hDcpS. RG3039 hydrochloride inhibits the decapping activity of DcpS and maintains DcpS in a catalytically inactive conformation in the central nervous system and other tissues. RG3039 hydrochloride extends survival and improves function in spinal muscular atrophy mice. RG3039 hydrochloride is applicable to research related to spinal muscular atrophy.
For research use only. We do not sell to patients.
- Purity: 98.15%
- CAS No.: 1466525-84-7
- Formula: C21H25Cl4N5O
- Molecular Weight:505.27
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Storage:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
RG3039 (1-100 nM) potently hydrochloride 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.
| Species | Dose | Route | Cmax | AUClast | AUC0-inf | CL/F | Tmax (Plasma) | AUCinf | Tmax (Brain) |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | p.o. | 25.6 (Plasma) ng/mL | 156.8 (Plasma) ng·h/mL | 285.8 (Plasma) ng·h/mL | 35153 (Plasma) mL/h/kg | 0.5 (Plasma) h | 7049 (Brain) ng·h/mL | 6.0 (Brain) h |
RG3039 (20 mg/kg; p.o.; once daily; postnatal day 11 to postnatal day 20) hydrochloride confers only a very weak survival benefit in 2B/2 SMA mice (median survival time: 23 days)[1].
RG3039 hydrochloride (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 No. 1466525-84-7
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Appearance Solid
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Molecular Weight 505.27
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Formula C21H25Cl4N5O
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Color White to light yellow
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SMILES
NC1=NC(N)=C2C(OCC3CCN(CC4=C(Cl)C=CC=C4Cl)CC3)=CC=CC2=N1.Cl.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Purity & Documentation
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Data Sheet (276 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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Handling Instructions (2659 KB)
References
[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;22(20):4084-4101. [Content Brief]
[2]. Van Meerbeke JP, et al. The DcpS inhibitor RG3039 improves motor function in SMA mice. Hum Mol Genet. 2013;22(20):4074-4083. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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