K-757
K-757 is an orally active, gut-targeted GPR40 agonist with EC50 values of 2.1 nM, 5.6 nM, 4.2 nM and 166 nM in humans, mice, rats and dogs, respectively. K-757 activates nutrient receptors co-expressed on pancreatic β cells and intestinal enteroendocrine cells. K-757 mediates and induces the secretion of satiety hormones GLP-1 and PYY in multiple in vitro and in vivo models. When used in combination with GPR119 agonist K-833, K-757 acts as a potentiator to elevate circulating levels of satiety hormones. K-757 can be used in the research of type 2 diabetes, weight loss and other related metabolic disorders.
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- CAS. Nr.: 2696409-13-7
- Formel: C32H48NO4P
- Molecular Weight:541.70
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
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hGPR40 2.1 nM (EC50) |
Mice GPR40 5.6 nM (EC50) |
Rat GPR40 4.2 nM (EC50) |
Dog GPR40 166 nM (EC50) |
GLP-1 |
K-757 (1-30 μM; 2.5 h) induces concentration-dependent GLP-1 secretion in wild-type mouse colonic crypt cultures via GPR40 activation, with no activity observed in GPR40 knockout cultures[2].
K-757 (0.01-30 μM; 2.5 h) induces concentration-dependent GLP-1 and PYY secretion in human ileal crypt cultures, with maximal responses at 10 and 30 μM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | CLplasma | Vdss | T1/2 | Cmax | Bioavailability |
|---|---|---|---|---|---|---|---|
| Mice[2] | 3 mg/kg | p.o. | 11 mL/min/kg | 0.55 L/kg | 1.0 h | 43 nM | 1.7 % |
| Mice[2] | 1 mg/kg | i.v. | 11 | 0.55 L/kg | 1.0 h | / | / |
| Rat[2] | 10 mg/kg | p.o. | 4.1 mL/min/kg | 0.26 L/kg | 2.6 h | 116 nM | 0.8 % |
| Rat[2] | 1 mg/kg | i.v. | 4.1 mL/min/kg | 0.26 L/kg | 2.6 h | / | / |
| Dog[2] | 2 mg/kg | p.o. | 7.2 mL/min/kg | 0.53 L/kg | 11 h | 225 nM | 13 % |
| Dog[2] | 1 mg/kg | i.v. | 7.2 mL/min/kg | 0.53 L/kg | 11 h | / | / |
| Monkey[2] | 2 mg/kg | p.o. | 4.1 mL/min/kg | 0.41 L/kg | 8.1 h | 49 nM | 1.1 % |
| Monkey[2] | 1 mg/kg | i.v. | 4.1 mL/min/kg | 0.41 L/kg | 8.1 h | / | / |
K-757 (0.3-30 mg/kg; p.o.; single dose, co-administered with K-833 30 mg/kg) in combination with K-833 induces enhanced GLP-1 secretion in fasted C57BL/6J mice, with maximal efficacy achieved at a 3 mg/kg single dose of K-757[2].
K-757 (10 mg/kg; p.o.; single dose) induces sustained GLP-1 secretion in fasted male Beagle dogs for at least 5 hours postdose[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 10−12 weeks old)[2]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg; 60 mg/kg
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Administration:p.o.; single dose
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Result:Elicited dose-dependent increases in plasma GLP-1 levels 1 hour postdose.
Achieved maximal efficacy at 10 mg/kg, resulting in GLP-1 levels of ~100 pg/mL.
Induced no GLP-1 secretion at 60 mg/kg in GPR40 knockout mice.
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Animal Model:C57BL/6J (male, 10−12 weeks old)[2]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg (co-administered with K-833 30 mg/kg)
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Administration:p.o.; single dose
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Result:Resulted in enhanced GLP-1 secretion that plateaued at 3 mg/kg, reaching GLP-1 levels of ~90 pg/mL.
Achieved active GLP-1 levels of ~6 pg/mL when 30 mg/kg was combined with K-833 30 mg/kg.
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Animal Model:Beagle (male, >6 months old, 6−12 kg body weight)[2]
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Dosage:10 mg/kg
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Administration:p.o.; single dose
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Result:Resulted in significant elevation of plasma GLP-1 levels evident as early as 1 hour postdose.
Reached peak GLP-1 levels of ~90 pg/mL at 1.5 hours postdose.
Maintained elevated GLP-1 levels for at least 5 hours.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS. Nr. 2696409-13-7
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Molecular Weight 541.70
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Formel C32H48NO4P
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SMILES
COC1=CC=C(CCCC(C)(C)C)C(N2CCC(COC3=CC=CC([C@H](C4CC4)CP(O)(C)=O)=C3)CC2)=C1
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
K-757 Related Classifications
HY-175420 Related Classifications
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