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.
For research use only. We do not sell to patients.
- CAS No.: 2101206-49-7
- Formula: C19H13ClF3NO4S
- Molecular Weight:443.82
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[2]|
GPR40 6 nM (EC50) |
In Vitro
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. Further protocols information, click here.
In Vivo
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 No. 2101206-49-7
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Molecular Weight 443.82
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Research Protocol for Endocrine Diseases
Endocrine diseases often arise from disrupted hormone production, hormone signaling, or target-tissue responsiveness; for diabetes-focused endocrine disease models, insulin signaling regulates glucose uptake, hepatic glucose output, lipid metabolism, and β-cell compensation. Type 2 diabetes develops through interacting defects in insulin resistance, β-cell dysfunction, adipose inflammation, hepatic glucose overproduction, altered incretin signaling, and ectopic lipid metabolism. A major unresolved question is whether endocrine dysfunction is driven primarily by target-tissue insulin resistance, intrinsic β-cell failure, immune/inflammatory stress, or combined multi-organ failure that differs by disease stage.
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Human Islet Cell Culture
The method of preserving islets in vitro, with purified reduced immunogenicity. The steps are islet isolation, islet cell purification, in vitro determination of islet function and islet cell culture.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
Purity & Documentation
References
[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
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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