SAR441255
Based on 1 Customer Validation
SAR441255 is a GLP-1R/GCGR/GIPR agonist, with human EC50 values of 1.03 pM, 1.01 pM, and 0.73 pM, respectively. SAR441255 stimulates receptor activity and drives cAMP accumulation. SAR441255 can be used for the research of type 2 diabetes, obesity.
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- Pureza: 99.84%
- Fòrmula: C225H3555N57O63
- Peso molecular:4866.56
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Almacenamiento:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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
Actividad biológica
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GLP-1 1.03 pM (EC50) |
SAR441255 (30 min) acts as a potent, balanced agonist of human GLP-1R, GCGR, and GIPR in recombinant HEK293 cells, with EC50 values of 1.03 pM, 1.01 pM, and 0.73 pM respectively[1].
SAR441255 potently activates endogenous human GLP-1R in 1.1B4 pancreatic cells (EC50 27 pM), GCGR in primary human hepatocytes (EC50 2100 pM), and GIPR in human adipocytes (EC50 42 pM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Tmax |
|---|---|---|---|
| Monkey[1] | 11 μg/kg | s.c. | ~2 h |
SAR441255 (3-11 μg/kg; s.c.; once daily; 42 days) induces significant body weight loss and improves glycemic control in obese, diabetic Macaca fascicularis monkeys over 42 days of treatment[1].
SAR441255 (11 μg/kg; s.c.; single dose) achieves significant in vivo occupancy of GLP-1 receptors in the pancreas and glucagon receptors in the liver of lean cynomolgus monkeys[1].
SAR441255 (3-300 μg/kg; s.c.; once daily; 4 days) causes transient, dose-related increases in heart rate and slight, sustained decreases in systolic blood pressure in lean telemetered cynomolgus monkeys[1].
SAR441255 (0.3-30 μg/kg; s.c.) reduces body weight in a dose-dependent manner[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6NHsd (female, 25-week-old obese, diet-induced obesity model)[1]
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Dosage:0.3 μg/kg; 1 μg/kg; 3 μg/kg; 10 μg/kg; 30 μg/kg
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Administration:s.c.; twice daily; 28 days
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Result:Produced body weight changes versus baseline of +9.7% (0.3 μg/kg), +6.9% (1 μg/kg), +5.8% (3 μg/kg), -4.8% (10 μg/kg), and -14.1% (30 μg/kg), compared to +11.5% for vehicle controls.
Achieved statistically significant weight reduction at doses of 3 μg/kg or greater versus vehicle.
Lowered nonfasted blood glucose significantly at doses of 1 μg/kg or greater versus vehicle.
Reduced liver weight significantly in the 10 μg/kg (p < 0.001) and 30 μg/kg (p < 0.0001) groups versus vehicle.
Decreased mean serum ALT levels by 73% (10 μg/kg, p < 0.001) and 81% (30 μg/kg, p < 0.0001) versus obese controls.
Reduced mean AST levels by 46% (3 μg/kg, p < 0.001), 55% (10 μg/kg, p < 0.0001), and 58% (30 μg/kg, p < 0.0001) versus obese controls.
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Animal Model:Macaca fascicularis (male, obese, diabetic)[1]
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Dosage:3 μg/kg; 5 μg/kg; 8 μg/kg; 11 μg/kg
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Administration:s.c.; once daily; 42 days
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Result:Produced a mean body weight reduction of -12.6% versus stable weight in vehicle-treated monkeys over 42 days (p < 0.05).
Decreased HbA1c levels by -1.37% (p < 0.05), reaching normoglycemic levels (<5%) at study end.
Lowered fasting plasma glucose and ALT levels significantly versus vehicle.
Showed a non-significant trend toward increased total ketones and 3-hydroxybutyrate levels at study end.
Caused a non-significant increase in FGF21 levels versus vehicle.
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Animal Model:Macaca fascicularis (lean)[1]
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Dosage:11 μg/kg
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Administration:s.c.; single dose
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Result:Produced a mean 40.6% decrease in liver radiotracer binding (indicating GCGR occupancy) versus baseline scans.
Achieved a mean 72.5% decrease in pancreatic radiotracer binding (indicating GLP-1R occupancy) versus baseline scans.
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Animal Model:Macaca fascicularis (4 males, 2 females, 3.12-6.10 kg, 37-51 months old, lean, telemetered)[1]
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Dosage:3 μg/kg; 30 μg/kg; 300 μg/kg
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Administration:s.c.; once daily; 4 days
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Result:Induced a dose-related increase in heart rate on day 1, lasting 10-11 hours for 3 μg/kg and 30 μg/kg doses, and up to 20 hours for 300 μg/kg dose.
Resolved heart rate increase in 3 μg/kg and 30 μg/kg groups by day 4, while it remained slightly elevated in 300 μg/kg group until day 5.
Caused no significant dose-related systolic blood pressure changes on day 1.
Induced a statistically significant, slight (<10 mmHg) decrease in systolic blood pressure lasting over 24 hours across all doses on day 4, with values remaining significantly below vehicle in 30 μg/kg and 300 μg/kg groups on day 5.
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Animal Model:Mice (diet-induced obese)[2]
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Dosage:0.3 μg/kg; 1 μg/kg; 3 μg/kg; 10 μg/kg; 30 μg/kg
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Administration:s.c.
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Result:Produced dose-dependent changes in body weight relative to vehicle-treated mice (which had a +11.5% body weight change): +9.7% at 0.3 μg/kg, +6.9% at 1 μg/kg, +5.8% at 3 μg/kg, -4.8% at 10 μg/kg, and -14.1% at 30 μg/kg.
Lowered non-fasted blood glucose levels significantly in mice treated at doses of ≥1 μg/kg compared with vehicle-treated controls.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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Appearance Solid
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Peso molecular 4866.56
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Fòrmula C225H3555N57O63
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Color White to off-white
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Sequence Shortening
H-{Aib}-HGTFTSDLSKL-{Lys(γGlu-γGlu-Palm acid)}-EEQRQ-{Aib}-EFIEWLKA-{d-Ala}-GPPS-{Aib}-KPPPK-NH2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvente y solubilidad
DMSO : 50 mg/mL (10.27 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 (sealed storage, away from moisture). 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 (sealed storage, away from moisture). 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)
Pureza y Documentación
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Ficha de datos (296 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
[1]. Bossart M, et al. Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist. Cell Metab. 2022;34(1):59-74.e10. [Content Brief]
[2]. Araki E, et al. Potential of a glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor/glucagon receptor triagonist for the treatment of obesity and type 2 diabetes. J Diabetes Investig. 2022 Dec;13(12):1958-1960. [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 (sealed storage, away from moisture). 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 | 0.2055 mL | 1.0274 mL | 2.0548 mL | 5.1371 mL |
| 5 mM | 0.0411 mL | 0.2055 mL | 0.4110 mL | 1.0274 mL | |
| 10 mM | 0.0205 mL | 0.1027 mL | 0.2055 mL | 0.5137 mL |
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