CCG-203586
CCG-203586 is a brain-penetrant glucosylceramide synthase (GCS) inhibitor. CCG-203586 reduces GCS production and brain levels, blocks the first committed step in ganglioside biosynthesis, and lowers downstream ganglioside levels. CCG-203586 can be used for the research of Tay-Sachs, Sandhoff disease, and types 2 and 3 Gaucher disease.
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- CAS. Nr.: 1430611-23-6
- Formel: C26H32N2O4
- Molecular Weight:436.55
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Speicherung:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Biologische Aktivität
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Chemical Information
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
CCG-203586 (Compound 2) (1 h) inhibits glucosylceramide synthase activity in MDCK cell homogenates with an IC50 of 27 nM[1].
CCG-203586 (24 h) reduces glucosylceramide levels in intact MDCK cells with an IC50 of 15.3 nM[1].
CCG-203586 (1 μM) has a half-life of 2.5 min when incubated with CD-1 mouse liver microsomes[1].
CCG-203586 (1 μM) has a half-life of 28 min when incubated with human liver microsomes[1].
CCG-203586 (Compound 3h) (24 h) inhibits glucosylceramide production in MDR1-MDCKII cells with an IC50 of 24.3 nM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | AUC0-∞ (Brain) | AUC0-∞ (Plasma) |
|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 36 h·ng/g | 317 ng·h/mL |
CCG-203586 (Compound 3h) (10-60 mg/kg/day; i.p.; 3 days) produces a dose-dependent reduction in brain glucosylceramide levels in healthy C57BL/6 mice, with concurrent significant reductions in kidney and liver glucosylceramide at the higher dose[2].
CCG-203586 (60 mg/kg; i.p.; daily; 7 days) administered to juvenile Sandhoff mice significantly reduces ganglioside (GM2, total sialic acid) and GA2 storage in brain and liver, with a 41% reduction in liver glucosylceramide, while showing no adverse effects on brain development or body weight[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (6−8 weeks old, mixed gender)[1]
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Dosage:60 mg/kg
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Administration:i.p.; daily; 3 days
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Result:Induced a 17% reduction in brain glucosylceramide levels relative to vehicle control.
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Animal Model:C57BL/6 (6- to 8-week-old, female or male)[2]
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Dosage:10 mg/kg/day; 60 mg/kg/day
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Administration:i.p.; daily; 3 days
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Result:Reduced brain GlcCer levels by 10% at 10 mg/kg/day compared to vehicle controls.
Reduced kidney GlcCer levels significantly at 10 mg/kg/day compared to vehicle controls.
Caused no significant change in liver GlcCer levels at 10 mg/kg/day compared to vehicle controls.
Reduced brain GlcCer levels by 17% at 60 mg/kg/day compared to vehicle controls.
Reduced liver and kidney GlcCer levels significantly at 60 mg/kg/day compared to vehicle controls.
Was well tolerated at both doses with no observed weight loss or adverse behavioral, gastrointestinal, or respiratory changes.
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Animal Model:SV/129 Hexb-/- (Sandhoff) (juvenile, postnatal day 9 to 15, Sandhoff disease model via Hexb gene disruption via homologous recombination and embryonic stem cell technology)[3]
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Dosage:60 mg/kg
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Administration:i.p.; daily; 7 days
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Result:Reduced total ganglioside sialic acid by 11% in cerebrum (to 432 μg/100 mg dry weight), 14% in cerebellum (to 318 μg/100 mg dry weight), and 38% in liver (to 70 μg/100 mg dry weight) relative to PBS-treated controls.
Reduced GM2 content by 52% in cerebrum (to 12.3 μg sialic acid/100 mg dry weight) and 53% in cerebellum (to 9.8 μg sialic acid/100 mg dry weight); reduced liver NGNA-GM2 by 45% (to 42.1 μg sialic acid/100 mg dry weight).
Reduced GA2 content significantly in cerebrum (to 0.51 mg/100 mg dry weight) and cerebellum (to 0.55 mg/100 mg dry weight) relative to controls.
Reduced liver glucosylceramide (GlcCer) by an average of 41% (to an average of 3.27 μg/100 mg dry weight) relative to controls.
Showed no significant difference in brain weight, brain water content, β-hexosaminidase specific activity, β-galactosidase specific activity, and cholesterol/neutral/acidic phospholipid distribution from PBS-treated controls.
Resulted in slightly higher body weight of treated mice (9.0 g) compared to PBS-treated Hexb-/- controls (7.8 g) and comparable to normal Hexb+/- mice.
Chemical Information
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CAS. Nr. 1430611-23-6
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Appearance Solid
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Molecular Weight 436.55
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Formel C26H32N2O4
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SMILES
[C@@H]([C@@H](CN1CCCC1)NC(CC2CC=3C(C2)=CC=CC3)=O)(O)C=4C=C5C(=CC4)OCCO5
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Reinheit & Dokumentation
Verweise
[1]. Wilson MW, et al. Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3. ACS Chem Neurosci. 2020;11(20):3464-3473. [Content Brief]
[2]. Larsen SD, et al. Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain. J Lipid Res. 2012;53(2):282-291. [Content Brief]
[3]. Arthur JR, et al. Ethylenedioxy-PIP2 oxalate reduces ganglioside storage in juvenile Sandhoff disease mice. Neurochem Res. 2013;38(4):866-875. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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