MK-2305
MK-2305 is an orally active GPR40 partial agonist with an EC50 of 6 nM in rats. MK-2305 mediates glucose-stimulated insulin secretion and inhibits endogenous glucose production by reducing gluconeogenesis from tricarboxylic acid (TCA) cycle substrates. MK-2305 increases plasma insulin levels under hyperglycemic and glucose-stimulated conditions, reduces fasting blood glucose, and improves glucose homeostasis. MK-2305 can be used in studies related to type 2 diabetes.
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- CAS. Nr.: 2101206-49-7
- Formel: C19H13ClF3NO4S
- Molecular Weight:443.82
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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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GPR40 6 nM (EC50) |
MK-2305 (60 min) potently and selectively activates rat GPR40 in CHO cells with an EC50 of 6 nM and 166% partial activation, while showing minimal activity against other metabolic receptors[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MK-2305 (10-30 mg/kg/day; p.o.; daily via diet; 20 days) reduces both fed and fasting blood glucose, lowers HbA1c, and enhances glucose-stimulated insulin secretion in male GK rats, with a 30 mg/kg/day dose producing a 30% reduction in fasting glucose on day 14[1].
MK-2305 (10 mg/kg; p.o.; single dose; 10 mg/kg/day; p.o.; daily) reduces endogenous glucose production in male GK rats, primarily through suppression of gluconeogenesis, with acute treatment lowering total EGP by 36.7%[1].
MK-2305 (10 mg/kg; p.o.; single dose) does not enhance glucose uptake in skeletal muscle or liver of male GK rats, instead reducing hepatic glucose disposal into glycogen and glycolytic products[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Goto Kakizaki (GK) (male, 8 weeks of age)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; single dose
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Result:Reduced glucose AUC during OGTT by 18% at 0.3 mg/kg, 40% at 3 mg/kg, and 54% at 10 mg/kg.
Increased insulin AUC by 59% at 1 mg/kg, 83% at 3 mg/kg, and 124% at 10 mg/kg.
Identified maximally efficacious dose (MED) as 3 mg/kg.
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Animal Model:Goto Kakizaki (GK) (male, 8 weeks of age)[1]
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Dosage:10 mg/kg/day; 30 mg/kg/day
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Administration:p.o.; daily via diet; 20 days
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Result:Reduced fed blood glucose by 22% at 10 mg/kg and 27% at 30 mg/kg on day 3, with effects maintained through day 20.
Reduced fasting blood glucose by 19% at both doses on day 7, and by 26% at 10 mg/kg and 30% at 30 mg/kg on day 14.
Reduced HbA1c levels at both doses.
Increased plasma insulin levels during OGTT on day 13 compared to vehicle controls.
Reduced food intake through day 14 at 30 mg/kg, with no sustained effect on body weight; 10 mg/kg dose had no effect on food intake or body weight.
Caused no significant changes in fasting plasma insulin, plasma non-esterified fatty acids, or liver triglycerides.
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Animal Model:Goto Kakizaki (GK) (male, 8 weeks of age)[1]
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Dosage:10 mg/kg; 10 mg/kg/day
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Administration:p.o.; single dose; p.o.; daily
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Result:Acutely reduced total endogenous glucose production (EGP) to 32.9 μmol/kg/min, a 36.7% reduction.
Acutely reduced EGP from gluconeogenic substrates entering at the TCA cycle to 26.0 μmol/kg/min.
Acutely reduced EGP from gluconeogenic substrates entering as triose phosphates to 6.90 μmol/kg/min.
Chronically reduced total EGP and EGP from TCA cycle substrates at 10 mg/kg/day.
Caused no effect on EGP derived from glycogenolysis.
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Animal Model:Goto Kakizaki (GK) (male, 8 weeks of age)[1]
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Dosage:10 mg/kg
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Administration:p.o.; single dose
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Result:Produced no significant effect on the disposal of 13C-glucose into metabolites in skeletal muscle.
Significantly reduced the disposal of 13C-glucose into 13C-glucose-6-phosphate, 13C-glycogen, 13C-lactate, and 13C-alanine in the liver.
Chemical Information
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CAS. Nr. 2101206-49-7
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Molecular Weight 443.82
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Formel C19H13ClF3NO4S
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SMILES
O=C1SC(C(=O)N1)C2C3=CC=C(OC4=CC=C(C=C4Cl)C(F)(F)F)C=C3OCC2
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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
[1]. Miller C, et al. GPR40 partial agonist MK-2305 lower fasting glucose in the Goto Kakizaki rat via suppression of endogenous glucose production. PLoS One. 2017;12(5):e0176182. Published 2017 May 23. [Content Brief]
[2]. Zhong YL, et al. Highly Enantioselective Rhodium-Catalyzed Transfer Hydrogenation of Tetrasubstituted Olefins: Application toward the Synthesis of GPR40 Agonist MK-2305. Org Lett. 2022;24(17):3254-3258. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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